tbuckley/cabot-search huggingface dataset:
Characteristics and outcome of patients with MYD88 wild-type Waldenström Macroglobulinemia.
Authors: Saurabh Zanwar, Jithma P. Abeykoon, Stephen M. Ansell, Jonas Paludo, Morie A. Gertz, Carrie A. Thompson, Rebecca L. King, Rong He, Nora N Benanni, Wilson I. Gonsalves, Grzegorz S. Nowakowski, Eli Muchtar, Rahma M. Warsame, Robert A. Kyle, Shaji Kumar, Prashant Kapoor
Journal: Journal of Clinical Oncology (2020)

8550 Background: Waldenström Macroglobulinemia (WM) is a rare lymphoplasmacytic malignancy characterized by the presence of a recurrent point mutation in the MYD88 gene (MYD88 L265P ) in 80-95% of cases. Patients with MYD88 WT genotype comprise a small subset that responds poorly to ibrutinib and other Bruton tyrosine kinase inhibitors. We examined the characteristics and outcome of WM patients with MYD88 WT genotype predominantly treated with non-BTK inhibitor based therapies. Methods: Patients with a diagnosis of WM seen at Mayo Clinic, Rochester, between 1996 and 2018 were included. Their characteristics and outcomes were assessed from the time of active disease. Marrow MYD88 genotyping was assessed with an allele specific PCR assay (analytic sensitivity 1%). Categorical and continuous variables were compared using Chi square and Wilcoxon tests, respectively. Time-to-event analyses were performed using Kaplan Meier test. Results: Of 986 patients with active WM, MYD88 genotype data were available in 331 (34 %) patients; 72 (22%) and 260 (78%) patients harbored MYD88 WT and MYD88 L265P genotypes, respectively. The median follow-up was 5.8 years (95% CI: 5.0-6.5 years) from active WM; 6 years MYD88 WT vs 5.4 years for MYD88 L265P cohort. Median age was 63 years and 66 years in the MYD88 WT and MYD88 L265P cohorts, respectively (p = 0.07) with 46% and 53% patients being ≥65 years of age, respectively (p = 0.36). Pre-treatment marrow lymphoplasmacytic (LPL) infiltrate (median 40% for MYD88 WT vs 60% for MYD88 L265P ; p = 0.001) and beta-2 microglobulin (median 3 µg/mL for MYD88 WT vs 3.9 µg/mL for MYD88 L265P ; p = 0.02) were lower in the MYD88 WT compared to the MYD88 L265P cohort; other laboratory parameters at active disease were comparable. Per IPSSWM prognostic criteria, MYD88 WT had fewer patients in the high risk group (18% for MYD88 WT vs 42% MYD88 L265P ; p = 0.03). Patients with MYD88 WT had higher likelihood of histological transformation [18% for MYD88 WT vs 4% for MYD88 L265P ; odds ratio 5.8 (95% CI: 2.5-13.5; p &lt; 0.0001)]. Among patients with treatment data available, only 35 (11%) patients received ibrutinib. The 5-year overall survival (OS) from active disease was comparable (85% in MYD88 WT vs 82% in MYD88 L265P cohort; p = 0.7). Conclusions: MYD88 WT genotype in WM is associated with lower marrow LPL infiltration, lower likelihood of high-risk IPSSWM categorization and a higher likelihood of histological transformation in comparison to MYD88 L265P mutant subpopulation. MYD88 genotype does not affect the OS from active disease in predominantly non-BTK inhibitor treated patients.
Neoadjuvant chemotherapy regimens for triple-negative breast cancer: Insights from network meta-analysis.
Authors: Hirotaka Miyashita, Christina Cruz, Stephen C. Malamud
Journal: Journal of Clinical Oncology (2020)

e12635 Background: The best regimen for neoadjuvant chemotherapy for triple-negative breast cancer (TNBC) is unknown. Recent studies have shown promising data that adding carboplatin improves the rate of pathological complete response (pCR) in TNBC). Therefore, we performed a network meta-analysis to define the overall most effective neoadjuvant systemic therapy for TNBC. Methods: We searched MEDLINE, Cochrane Library, and EMBASE from inception to December 2019 for studies comparing the efficacy of different neoadjuvant regimens in patients with TNBC. We performed a network meta-analysis comparing the regimens in the selected studies using the random-effects model. We focused on anthracycline (A), bevacizumab (B), everolimus (E), and platinum salts (Pl) because these are the medications commonly added to taxane based regimens. All studies contained a taxane regimen. We analyzed the rate of pCR (ypT0/is, N0) and the incidence of grade 3-4 neutropenia, thrombocytopenia, nausea/vomiting, and diarrhea. Results: We identified a total of 13 randomized control trials for this analysis. We compared eight different classes of regimens. We found that regimens containing Pl were significantly superior to Pl non-containing regimens for the rate of pCR. (risk ratio (RR) for pCR [95% confidence interval (CI)]: 1.66 [1.19-2.31], 1.37 [1.14-1.64], and 1.36 [1.14-1.62] for no medications of special interest vs Pl, A vs A+Pl, and A+B vs A+B+Pl, respectively). Regimens containing B were associated with a significantly better rate of pCR. (RR for pCR [95% CI]: 1.24 [1.06-1.46] and 1.23 [1.01-1.51] for A vs A+B and A+Pl vs A+B+Pl, respectively) In contrast, adding A into the regimen did not improve the rate of pCR. In the safety analysis, regimens containing Pl were associated with a significantly higher incidence of grade 3-4 neutropenia and thrombocytopenia. Regimens containing B showed a higher incidence of grade 3-4 nausea/vomiting, and diarrhea. Conclusions: For TNBC, adding Pl or B into the neoadjuvant therapy regimen brings about a higher pCR rate, though they are associated with an increase in hematologic or gastrointestinal complications. The benefit of adding A to the neoadjuvant chemotherapy regimen for TNBC is not apparent.
Association of time interval from neoadjuvant chemotherapy to interval cytoreduction and interval cytoreduction to adjuvant chemotherapy with survival outcomes and risk of platinum resistance.
Authors: Viviane Alencar, Rafaela Pirolli, Felipe Leonardo Estati, Adriana Regina Goncalves Ribeiro, Andrea Paiva Guimaraes, Glauco Baiocchi, Alexandre Andre B. A. Da Costa
Journal: Journal of Clinical Oncology (2020)

e18043 Background: Neoadjuvant chemotherapy (NACT), followed by interval debulking surgery (IDS), is a possible approach to patients with stages IIIC and IV epithelial ovarian cancer who are most likely to have suboptimal results with upfront surgery. Delay in initiation of adjuvant chemotherapy has been associated with worse outcomes. Our study aimed to evaluate whether time from NACT to surgery (TNS) and from surgery to adjuvant chemotherapy (TSA) were associated with survival outcomes and with platinum-resistant relapse. Methods: We did a retrospective analysis of medical records from 194 patients with EOC treated with IDS at a single institution from 2007 to 2018. We calculated the median TNS and TSA and evaluated its relation to progression free survival (PFS), overall survival (OS) and time to platinum-resistant relapse (TTPR) through Kaplan-Meier and Cox regression analysis. Results: After a median follow-up of 62 months, OS was 58 months and PFS was 18 months. Most patients received at least 3 cycles of NACT (21.1% 3 cycles, 16.0% 4 cycles and 39.7% 6 cycles); and the rate of optimal cytoreduction was 75,8%. Optimal surgery was associated with survival (p &lt; 0.001). TNS over 8 weeks and TSA over 7 weeks were associated with worse PFS (HR 1.57, 95%CI 1.07-2.31; HR 1.52, 95%CI 1.00-2.32, respectively) and OS (HR 1.83, 95%CI 1.13-2.96; HR 1.57, 95%CI 0.93-2.65, respectively) in univariate analysis but not in a multivariate analysis including residual disease as a covariate. In the subgroup of patients with residual disease &lt; 10mm a multivariate analysis showed shorter PFS (HR 2.06, CI95% 1.16-3.66, p = 0.014) and OS (HR 2.20, CI95% 1.05-4.59, p = 0.035) for patients with TSA longer than 7 weeks. Longer TNS was associated with PFS (HR 1.66, 95%CI 1.06-2.59, p = 0.026) in univariate analysis but not in multivariate analysis. Interestingly, longer TNS was associated with shorter TTPR (65.6 vs. 35.0 months, p = 0.049) and a higher frequency of platinum resistant relapse at first relapse (48.8% versus 26.5%, p = 0.012). Conclusions: Our study provides evidence that delayed TSA is an independent prognostic factor for worse PFS and OS only in the subgroup of patients with residual disease ≤ 10mm. Longer TNS was associated with higher risk of platinum resistant relapse. One possible explanation is that NACT may select chemoresistant clones, which would have more time to grow and spread with longer intervals until surgery. Further studies are necessary to corroborate this hypothesis.
肺癌合并肺大疱误诊一例
Authors: 游庆军, 金小寅, 蒋锡初
Journal: BMJ (2005)

患者男,67岁,因发热咳嗽半月余入院.体格检查:双侧锁骨上淋巴结无肿大,右上肺叩诊呈鼓音,未闻及呼吸音.X线胸片示:右侧气胸(肺压缩35%),右上肺包裹性积液,局部肺不张.于右胸上部置管一根,引流出大量气体及淡黄色积液160 ml,3 d后复查胸片右上肺仍不张,遂于全麻下行右侧剖胸探查术.术中见右上肺数个肺大疱,最大的一枚直径为10 cm,1枚破裂,右上肺近肺门处扪及直径6 cm肿块,且肺门、隆突下、上纵隔处探及多个融合肿大淋巴结,判断肺癌可能性大,故切除右上肺叶并清扫纵隔淋巴结.术后病理:右上肺中央型腺癌Ⅱ级合并鳞癌Ⅱ级,周围淋巴结查见癌转移(7/14)。
Relevance of bone marrow biopsies for response assessment in NCTN follicular lymphoma clinical trials.
Authors: Sarah C. Rutherford, Jun Yin, Levi Pederson, Betsy LaPlant, Mazyar Shadman, Hongli Li, Michael Leo LeBlanc, Kristie A. Blum, Travis Dockter, Peter Martin, Sin-Ho Jung, Barbara W. Grant, Cara Ann Rosenbaum, Chaitra Shankar Ujjani, Paul M. Barr, Joseph M. Unger, Bruce D. Cheson, Nancy L. Bartlett, Jonathan W. Friedberg, John Paul Leonard
Journal: Journal of Clinical Oncology (2020)

8038 Background: Bone marrow biopsies (BMB) are performed pre/post therapy to confirm complete response (CR) in patients (pts) with lymphoma on clinical trials. We evaluated 2 prior data sets and concluded that BMB impact response assessment in a minority of pts with follicular lymphoma (FL) (Rutherford BJH 2017; Rutherford ASH abstract 1605, 2018). We sought to establish if BMB add value in assessing response or identify distinct progression free (PFS) or overall survival (OS) outcomes in a large, multicenter, multi-trial cohort. Methods: Data were pooled from 7 trials of 580 pts with untreated FL conducted through the Alliance for Clinical Trials in Oncology and SWOG from 2002-2016. The proportion of pts with positive (+) baseline BMB, CR on imaging after treatment, and (+) repeat BMB was calculated using total pts enrolled as the denominator. We tested against the null hypothesis that the proportion was = 10%, the threshold below which BMB would be considered irrelevant for response assessment, versus (vs) the alternative hypothesis that this proportion was &lt; 10%, using 1-sided exact binomial test. Response criteria were CT-based. Imaging was not used to assess BM involvement. Because confirmatory BMB were not completed in all indicated pts, landmark survival analyses compared PFS/OS of pts with CR on imaging and negative (-) BMB vs pts with CR on imaging without repeat BMB. Pts with CR on imaging were categorized as having (-) repeat BMB or no repeat BMB within 60 days of first CR on imaging. PFS and OS were calculated from time of first CR and estimated using Kaplan-Meier and Cox models adjusting for age, sex, stage, Follicular Lymphoma International Prognostic Index (FLIPI) score, and treatment type (targeted vs chemotherapy plus targeted therapy), and stratified by treatment arm. Results: Median age was 55 with 51% male, 96% stage III-IV, and 88% grade I-II. FLIPI scores were 113 low, 265 intermediate, and 199 high risk. 67% received chemotherapy-based regimens. Baseline BMB was (+) in 321 (55%). Only 5/580 (0.8%) had (+) baseline BMB, CR on imaging, and subsequent (+) BMB (p &lt; 0.0001). Of pts with CR on imaging, PFS and OS were not different among pts with (-) BMB vs pts without repeat BMB (PFS: HR = 1.08, 95%CI 0.61-1.93, p = 0.783; OS: HR = 0.52, 95%CI 0.20-1.40, p = 0.199). Conclusions: BMB requirements may discourage pt participation in trials and add pain, expense and time without providing necessary information. We recommend eliminating BMB for response assessment from FL clinical trials. Clinical trial information: NCT00553501, NCT01145495, NCT01190449, NCT01286272, NCT01829568, NCT00822120, and NCT00770224 .
Treatment outcome and prognostic indicators in 26 cases of fibrolamellar hepatocellular carcinoma under interferon based therapy.
Authors: Yehia I. Mohamed, Aliya Qayyum, Manal Hassan, Lianchun Xiao, Dan G. Duda, Rikita Hatia, Sunyoung S. Lee, Robert A. Wolff, Jeffrey Morris, Lina Altameemi, James C. Yao, Hesham M. Amin, Ahmed Omar Kaseb
Journal: Journal of Clinical Oncology (2020)

e16626 Background: Fibrolamellar hepatocellular carcinoma (FLHCC) is a variant of HCC that comprises ∼1%–9% of all HCCs, with about 200 annual cases reported globally, most often affects younger patients (10–35 years of age) with no underlying liver disease. There is no current standard of care therapy for unresectable FLHCC. We report an analysis of the treatment outcomes, and prognostic indicators of 26 cases. Methods: We retrospectively collected clinicopathologic and treatment outcome data from 26 FLHCC patients who received interferon alfa-2b (IFN) based therapy. Median overall survival (OS) and PFS were calculated using Kaplan-Meier curves, and survival rates were compared by the log-rank test. Results: 21 patient underwent treatment with continuous infusion (CI) 5-Fluorouracil (FU) at 200 mg/m2/day for 7 days on, 7 days off plus IFN at 4 million units/m2, subQ every other day for 7 days on, 7 days off, 1 patient FU+IFN+bevacizumab and 4 patients had PIAF (cisPlatin+IFN+Adriamycin+FU). Median age was 24 years (15-44), 13 males and 13 females, 8 of the 26 patients died, the median overall survival was 33.9 months (95% CI, 20.9, NA), estimated 3-year survival was 20.2% (95% CI: 4.1%, 98.5%), median follow up time was 13.4 months (95% CI: 9.79, NA) and median progression-free survival was 11.7 months (95% CI: 5.09, NA). The estimated 1-year survival was 47.9% (95% CI: 29.9%, 76.8%). Finally, FU+IFN combination was the most frequently used systemic therapy. 3/26 pts underwent surgical resection following neoadjuvant treatment with interferon based therapy; Interferon based therapy for the 26 patients had limited side effects, with only 3 of the 26 patients discontinued treatment due to grade 3-4 adverse event in the form of mucositis, severe fatigue and/or hematologic toxicity. Conclusions: Our analyses indicate that CI FU + IFN could be an effective treatment for FLHCC, and may have a neoadjuvant role in this disease with 3/26 were resectable following neoadjuvant treatment with interferon based therapy. This regimen can be well tolerated. Unfortunately, nonsurgical options for patients with FLC remain limited with no approved local or systemic therapies. Therefore, future research is needed to identify better multimodality therapies.
Five year letrozole versus placebo in <i>BRCA1/2</i> germline mutations carriers: Final results of LIBER, a double-blind randomized phase III breast cancer prevention trial.
Authors: Pascal Pujol, Lise Roca, Alain Lortholary, Christine Lasset, Catherine Dugast, Pascaline Berthet, Isabelle Tennevet, Jean-Pierre Fricker, Chabbert-Buffet Nathalie, Paul Gesta, Pascale This, Jean Chiesa, TD N'Guyen, Audrey Mailliez, Laurence Venat-Bouvet, Hélène Dreyfus, Capucine Delnatte, Virginie Galibert, Jerome Lemonnier, Suzette Delaloge
Journal: Journal of Clinical Oncology (2020)

1534 Background: Women with germline BRCA1/2 (gBRCA1/2) mutations have a 70% lifetime risk of breast cancer (BC). Medical prevention by aromatase inhibitors is effective in high-risk patients (pts), including those with familial risk. However, hormone prevention has not been specifically addressed in women (wn) carrying gBRCA1/2 mutations. Methods: LIBER is a randomized, double-blind, placebo-controlled phase III trial evaluating 5-year treatment with letrozole 2.5 mg/day (L) versus placebo (P) on decreasing BC incidence in post-menopausal women with gBRCA1/2 mutations ( NCT00673335 ). Eligible wn were aged 40-70 and could have had unilateral BC &gt; 5 years ago. Randomization was stratified on mutation ( BRCA1/BRCA2), bilateral oophorectomy and history of prior BC. Primary endpoint was 5-year invasive BC-free survival (BC-FS) in wn with or without previous BC. Main secondary endpoints were safety and quality of life (menopause rating scale, SF36). 270 pts were required to observe 37 events to show a gain in 5-year invasive BC-FS from 80% to 92% (HR=0.35) with 1-sided α=0.05 and 90% power. Results: 170 wn were randomized from 02/2008 to 02/2013; 86 and 84 were assigned to the P and L arm. Median age was 55 years (range 40-70). Pt characteristics were well balanced; 59% and 41% carried gBRCA1 and gBRCA2 mutations. In P and L arms, 47% and 43% had prior BC, 43% and 42% stopped treatment prematurely, 37 and 23 serious adverse events occurred, and during active treatment, 8 and 10 wn had grade 3/4 toxicity. Median follow-up was 72.7 months. Five-year BC-FS did not significantly differ between the P and L arms (92% vs 91%, HR 0.83; 95%CI: 0.3-2.3, p=0.73) in the overall population, nor in the subgroups of wn with and without previous BC (74% vs 91%; HR 0.43; 95% CI: 0.1-1.3; 90% vs 86%; HR 1.29; 95% CI 0.4-3.9), gBRCA1 versus gBRCA2 or hormone receptor-positive BC. Letrozole had no effect on quality of life. The two groups did not significantly differ in bone density, which decreased over time in the overall population. Conclusions: In this prospective preventive trial, BC-FS was not significantly decreased by letrozole versus placebo in women with BRCA1/2 mutations. However, the study was underpowered (170 of 270 pts expected). Despite no differences in safety and quality of life, drop-out rate was high in both P and L arms. Clinical trial information: NCT00673335.
Morphology classification of circulating tumor cells could be a predictor of recurrent disease in patients with non-small cell lung cancer after surgery.
Authors: Yun Wu, Yuxu Niu, Fanzhen Lv, Wen Gao, Xiaoyong Shen
Journal: Journal of Clinical Oncology (2020)

e15530 Background: CTCs have been widely used in monitoring the efficacy and prognosis of lung cancer. However, CTCs number count alone cannot accurately predict the recurrent disease in patients. In this study, we investigate whether the morphology classification of CTCs could be as a prognostic marker for increased risk of recurrence after surgery. Methods: In this study, 105 lung cancer patients (median age 68y) who underwent surgery were prospectively enrolled in this study. Samples were obtained before, after, and serially up to 24 months after surgery. CTCs were collected and morphology classified by utilizing a CTC test workflow which uses negative enrichment and immunofluorescence methods to capture and identify CTCs from blood sample. Captured CTCs (epithelial type) were screened with a customized imaging analysis pipeline, a cytological profile of each CTC was created, including cell size, shape, fluorescent intensity and texture etc. Results: The CTC detection rate was 78.1% (78 of 105) prior to surgery, and a total of 726 CTCs were enumerated. Median CTC count number was 3. 5 classes of CTCs with distinct morphological features were observed in lung cancer patients’ CTC tests, briefly, CTC class I and class II possessed large nuclei but relatively lower epithelial expression level, CTC class III, IV, V possessed small nuclei but relatively higher epithelial expression level, CTC class III possessed irregular shaped nuclei, CTC class V possessed relatively lower nuclei/cytoplasm ratio. Class III accounted for the highest proportion of captured CTCs III, about 35.5% with Class I 14.8%, Class II 15.3%,Class IV 17.8% and Class 5 16.6%. Postoperative recurrence and metastasis were observed in 16 patients. CTCs positive were found in 14 patients (87.5%). 145 CTCs were collected, Median CTC count number was 3,Cluster III accounted for 47.3%, with Class I 11.8%,Class II 13.3%,Class IV 14.5% and Class V 11.8%; Patients with Cluster 3 dominant were associated with increased risk of local recurrence ( p &lt; 0.05) and distant metastasis ( p &lt; 0.05). Conclusions: Small and irregular nuclei CTC is significant associated with increased risk of recurrence disease. Morphology Classification of circulating tumor cells is feasible in monitoring the recurrence of disease and may potentially identify the patients who may benefit from further therapy.
The roles and challenges of primary care practitioners in prevention and control of the outbreak of COVID-19
Authors: Zhijie Xu, Yiting Lu, Lizheng Fang
Journal: BMJ (2020)

Since December 2019, the outbreak of Coronavirus disease 2019 (COVID-19) has rapidly swept across the country, posing great challenges to the public health in China. In the epidemic prevention and control, primary care practitioners play a very important role in patient triage, home-based visit, follow-up as well as screening at the checkpoints. However, due to the lack of necessary protective equipment and heavy workload, primary care practitioners are facing great challenges in containing the epidemic outbreak. Based on the relevant guidelines and practice in primary care, this article summarizes the challenges primary care practitioners encountered and coping strategies for containing the epidemic outbreak in primary care settings to provide reference for improvement of their working quality.

Key words: 
Coronavirus infection; Coronavirus disease 2019; Community health service center; Primary physicians
An analysis for awareness of knowledge about chronic obstructive pulmonary disease and effectiveness of training among rural practitioners in Haiyang, Shandong
Authors: De-qi Zou, Xue-shun Zhang, Hai Gao, Jian-ling Wang
Journal: BMJ (2010)

Objective To understand awareness of basic concepts, diagnosis, treatment and patient education for chronic obstructive pulmonary disease (COPD) among practitioners in rural new cooperative medical scheme (NCMS) and evaluate effectiveness of training for them in Haiyang, Shandong.Methods In total, 116 practitioners, two or three randomly selected from each of 43 NCMS service stations under the Third People's Hospital of Haiyang, were surveyed with questionnaire and then systematic training was provided for them. Another survey was conducted among them a half and two years after the first one with the same questionnaire. Results At the first survey, only 9.5 % (11/116) of the practitioners surveyed knew about  for Prevention and Control of Chronic Obstructive Pulmonary Disease,19. 8 % (23/116) knew clinical characteristics of COPD, 29. 3 % (34/116) knew that pulmonary function test is gold standard for COPD diagnosis, 62. 9 % (73/116) knew that smoking is major inductive factor for COPD and could persuade patients to quit smoking, only 2.6 % (3/116) could make registration for the patients and provide health education for them, 48. 3 % (56/116) knew that the patients should be immunized with influenza vaccine, and 7. 8 % (9/116) knew long-term oxygen therapy for the patients. At the second survey, 94. 8 % (110/116) of the practitioners surveyed knew about  Guidelines for Prevention and Control of Chronic Obstructive Pulmonary Disease, all of them knew characteristics of COPD, that pulmonary function test is gold standard for COPD diagnosis, smoking is major inductive factor for COPD,could make registration for COPD patients and provide health education for them, 99. 1% (115/116) used influenza vaccine for COPD patients, and 99. 1% (115/116) knew long-term oxygen therapy for the patients. Conclusions Systematic training for COPD knowledge among practitioners in rural NCMS seems to be significantly beneficial for their awareness about the illness and to improve their abilities of prevention and treatment for it in rural areas.

Key words: 
Pulmonary disease ,chronic obstructive ; Rural health services;  Questionnaires