tbuckley/cabot-search huggingface dataset:
Paclitaxel-induced peripheral neuropathy in early-stage breast cancer patients.
Authors: Jacqueline Liu, Hormozan Sorooshian
Journal: Journal of Clinical Oncology (2020)

e12503 Background: Peripheral neuropathy is a major dose-limiting side effect of paclitaxel and can persist for up to two years after completing treatment, greatly affecting both the course of chemotherapy and quality of patients. Few studies have characterized the side effect profiles of two commonly used paclitaxel-based adjuvant regimens, dose-dense biweekly paclitaxel with growth factor support (ddP, 175 mg/m2 biweekly for four cycles) and weekly paclitaxel (wP, 80 mg/m2 weekly for 12 cycles). Conflicting results exist regarding the incidence of paclitaxel-induced neuropathy related to either administration scheme. Methods: This is a data-only retrospective cohort study that consisted of adult patients with early-stage breast cancer who received either ddP or wP at Kaiser Permanente Diablo Service Area (Walnut Creek and Antioch Medical Centers) between January 1, 2010 and January 1, 2019. The primary endpoint was the proportion of patients with dose-limiting chemotherapy-induced peripheral neuropathy (DL CIPN). Results: 244 patients were included in the final analysis with 159 and 85 patients receiving wP and ddP, respectively. Baseline demographics were well matched between the two groups. There was no significant difference in the proportion of patients who experienced DL CIPN with wP (17.6%) compared to ddP (19.1%) (p = 0.647). Grade 3 or 4 adverse events occurred in 8.9% of patients who received wP and 10.6% of patients who received ddP. No significant difference was observed (p = 0.650). Conclusions: The results of this study support the current National Comprehensive Cancer Network (NCCN) guidelines, which recommend dose-dense doxorubicin and cyclophosphamide (ddAC) followed by either sequential wP or sequential ddP with growth factor support as preoperative and/or adjuvant therapy for the treatment of early-stage breast cancer. The selection of an appropriate paclitaxel schedule is provider preference and largely based on the consideration of patient tolerability. These findings suggest that the concern for paclitaxel-induced peripheral neuropathy, including DL CIPN, may potentially play a smaller role in helping guide clinicians who are choosing between the two paclitaxel-based adjuvant regimens.
A tailored predication model to improve outcomes and mortality in geriatric indigenous women with breast cancer of western Australia.
Authors: Azim Khan, Hilary Laura Martin, Lisa Spalding, Andrew D. Redfern
Journal: Journal of Clinical Oncology (2020)

e14000 Background: Indigenous women with breast cancer (BrCa) have higher mortality than Non-Indigenous women. Remoteness, aggressive tumour biology, treatment acceptance and compliance are all contributory factors. A retrospective study of geriatric indigenous women (aged 55 years more) with BrCa has shown high co-morbidity and treatment-related toxicity scores translating to high mortality comparing to the non-indigenous geriatric population (aged 65 years or more). An algorithm allowing prediction of risk of morbidity and mortality to enable optimisation of care for this patient group, catering to needs, values, beliefs and resources of geriatric Indigenous patients is warranted. Methods: To create a predictive algorithm and model of care based on the demographics, social environment, biology, co-morbidity burden and predicted chemotherapy toxicity scores of Indigenous women with BrCa to then be applied to a validatory prospective study.A cohort of 132 indigenous geriatric patients was identified from the Western Australian Cancer Registry from 2001 to 2010 along with remoteness matched geriatric non-Indigenous women in a 1:1 ratio. Data was collated on cancer biology, chemotherapy toxicity, mortality, co-morbidity burden (by the Charlson Co-Morbidity Index -CCI) and predicted chemotherapy toxicity (by CARG toxicity score). An algorithm was created based on these factors to identify patients at greatest risk of morbidity and mortality. Results: Elements identified as predicting morbidity and mortality were; remoteness based on distance from Perth (scored 0-3), lymph node status (scored 0-1), social isolation (scored 0-1), the Carg score (scored 0-3), and the CCI (scored 0-4). The KR Geri-Indigenous Rx Model was created using these components and scored out of 12. Conclusions: The score has been used to create three risk categories, low (1-3) intermediate (4-8) and high risk (9-12). A model of care was designed with staged increases in service elements and intensity for increasing risk category. These include the addition of Indigenous health worker review initially in clinic as well as at home during chemotherapy, initial geriatric assessment and potential geriatrician review, optimization of co-morbidities and medications, consideration of dose adjustments, social worker visits to increase services, increased surveillance, with telehealth contact and GP update with treatment planning as well as on treatment completion. A prospective study based on this model is planned.
Evidence-based practice and evaluation for clinical effectiveness of traditional chinese medicine
Authors: 梁晓春
Journal: BMJ (2004)

中医药学有着非常悠久的历史,她以独特的理论体系和丰富的临床经验,为中华民族的繁衍昌盛做出了不可磨灭的贡献.随着时代的发展、科学的进步,中医传统的辨证施治以及单凭机体整体症状改善来观察临床疗效的方法受到了极大的冲击.循证医学(evidence based medicine,EBM)是遵循证据的医学,其核心就是任何医疗决策的确定,包括医生处理患者、专家制定治疗方案、政府制定医疗卫生政策等,都需建立在当前最佳的科学依据基础之上。
Patient characteristics and treatment patterns in relapsed/refractory multiple myeloma patients after exposure to a proteasome inhibitor, an immunomodulatory agent and daratumumab.
Authors: Maneesha Mehra, Martin Vogel, Satish Valluri, Sandhya Nair, Jordan Schecter, Sundar Jagannath, Katja Weisel, Saad Zafar Usmani
Journal: Journal of Clinical Oncology (2020)

e20540 Background: Many novel agents, such as a Chimeric Antigen Receptor T-Cell (CAR-T) therapy, are under investigation for the treatment of relapsed/refractory multiple myeloma (RRMM) patients (pts) who have been exposed to a proteasome inhibitor (PI), immunomodulatory drug (IMiD), and daratumumab (triple-exposed). However, limited data are available on treatment patterns in these pts. Here, we aim to study characteristics and treatment patterns after triple-exposure in RRMM pts. Methods: Data from triple-exposed RRMM pts from the Flatiron MM core registry (Jan 1, 2011 - Oct 2019) who received ≥3 prior lines of therapy (LOT) were used for the analyses. Descriptive statistics for pt characteristics and treatment patterns were assessed at end of triple exposure LOT (time T 0 ) and after triple exposure by LOT. Results: Of the 10,011 MM pts in the Flatiron registry, 1,029 were triple-exposed; of these, 362 had a LOT after triple-exposure. Median age at T 0 was 68 years and time to triple-exposure was 3.5 years from index MM diagnosis (Table). 52% were male, 81% (of 250 with available ECOG data) had ECOG status &lt; 2, and 54% had a stem cell transplant. In 96% of pts, daratumumab was part of the triple-exposure regimen. Median follow-up from triple-exposure (LOT end date) was 7.4 months. 49% and 23% of pts had ≥2 LOTs and ≥3 LOTs after triple-exposure. Pomalidomide-, carfilzomib-, or daratumumab-containing regimens accounted for 71% and 49% of all LOT1-post-triple and LOT3 post-triple treatments, respectively; non-novel treatments accounted for 18% and 30% of LOT1 post-triple and LOT3 post-triple treatments. Conclusions: Triple-exposed RRMM pts accounted for approximately 10% of the population in the Flatiron MM core registry. Triple-exposed RRMM pts progress to multiple LOT in which they continue to be treated with PIs, IMiDs, and daratumumab; therefore, there is a need for new treatments with novel mechanisms of action for this pt population. [Table: see text]
营养和运动治疗对妊娠糖尿病患者的影响
Authors: 王凤珍
Journal: BMJ (2007)

对34例初次就诊临床确诊为妊娠糖尿病的患者,采用营养和运动治疗.治疗后,33例患者空腹血糖、餐后2 h血糖、糖化血红蛋白、甘油三酯、总胆固醇水平正常或接近正常.1例患者未坚持治疗,血糖、血脂升高,分娩4700 g巨大儿.治疗满意率为97%.说明采用营养和运动治疗是保证母子健康的重要措施。
Integrated model of specialist-general practitioner and community nurse for diabetes management in Xinjiang primary care settings
Authors: Bin Huang, Xudong Ji, Shengyan Wang, Jianxin Yin, Naihong Yang, Junxia Zhai, Wenhuan Kang, Xuhong Ma, Jin Li
Journal: BMJ (2020)

A total of 115 patients with type 2 diabetes recruited from Quanzijie Township Health Service Center were divided into integrated management group (n=54) and specialist management group (n=61). Patients in integrated management group were managed by specialists, general practitioners (GPs) and community nurses jointly; while patients in specialist management group were managed by specialists only. Subjects were followed up every 4 weeks for 24 weeks. Total 366 person/time diabetes education courses were given to subjects in integrated management group during the intervention. After intervention, the fasting glucose, 2 h postprandial glucose and glycosylated hemoglobin were decreased significantly in both groups (P<0.05), while the triglyceride level in the integrated management group was significantly lower than that in the specialist management group (P<0.05). In conclusion, patients with type 2 diabetes managed by integrated mode can achieve similar glucose control effect as specialist management mode in primary care settings and their triglyceride level can be also significantly decreased.


Key words: 
Rural health services; Diabetes mellitus, type 2; Disease management
Pharmacokinetic tuning of protein–antigen fusions enhances the immunogenicity of T-cell vaccines
Authors: Naveen K. Mehta, Roma V. Pradhan, Ava P. Soleimany, Kelly D. Moynihan, Adrienne M. Rothschilds, Noor Momin, Kavya Rakhra, Jordi Mata-Fink, Sangeeta N. Bhatia, K. Dane Wittrup, Darrell J. Irvine
Journal: Nature Biomedical Engineering (2020)
Comorbidity burden in prostate cancer patients by ESRD status.
Authors: Nagaraju Sarabu, Weichuan Dong, Austin Fernstrum, Al Ray, Lee Evan Ponsky, Siran M. Koroukian
Journal: Journal of Clinical Oncology (2020)

e17510 Background: The co-occurrence of cancer and end-stage-renal disease (ESRD) may pose significant challenge in the management of both diseases. Further complicating clinical decisions is our limited understanding of the comorbidity burden (CB), which also affects their outcomes to a considerable extent. The purpose of this study is to characterize the CB in prostate cancer patients, with and without ESRD. Methods: Using SEER-Medicare database between years 2000-2016, we retrieved sociodemographic variables, including age (40-54, 55-64, 65-74, and 75+), race (African American vs. all others), marital status (married/partnered vs. all others), residence in a census tract with poverty rate &gt; 20%, and dual Medicare-Medicaid enrollment status; chronic conditions identified in the year of cancer diagnosis; and ESRD status preceding prostate cancer diagnosis. We limited our study population to cancer patients enrolled in Medicare at the time of cancer diagnosis, and were receiving their care through the fee-for-service system. In this descriptive analysis, we compared the prevalence of these conditions between prostate cancer patients by ESRD status. Results: Our study population included 2,046 ESRD and 302,136 non-ESRD men diagnosed with incident prostate cancer during the study period. Compared to non-ESRD patients, a disproportionately higher percentage of ESRD patients were in the 40-54 and 55-64 age groups compared to non-ESRD (11.0 vs 0.95% and 32.2% vs. 8.51%, respectively). Similarly, the percentage of prostate cancer patients who were African American was 44.1% among ESRD patients, compared with 13.6% in their non-ESRD counterparts. With regard to comorbidities, several conditions were significantly higher in ESRD than non-ESRD patients, including: anemia (65.4% vs. 15.3%), congestive heart failure (31.1% vs. 8.9%), ischemic heart disease (38.9% vs. 25.2%), diabetes (40.7% vs. 17.0%), hypertension (68.0% vs. 42.6%), hypothyroidism (4.6% vs. 2.9%), hyperlipidemia (43.1% vs. 35.1%), and stroke (3.7% vs. 2.5%). Conclusions: Compared to their non-ESRD counterparts, ESRD patients present with high CB, severely compromising their physiologic reserve and tolerance for various cancer treatment modalities, and affecting outcomes. Future studies should compare the prevalence of specific combinations of conditions constituting multimorbidity between ESRD and non-ESRD patients, and identify multimorbidity profiles associated with a lower likelihood to receive standard treatment. Such detailed analysis will be foundational to clinical management and outcome studies.
Keeping oncologists current with CDK4/6 inhibitors in HR+ breast cancer: The impact of online education.
Authors: Kinjal Parikh, Mindy Tanzola, Pamela M. Peters, Massimo Cristofanilli
Journal: Journal of Clinical Oncology (2020)

e13044 Background: CDK4/6 inhibitors have revolutionized the care of patients with hormone receptor positive (HR+), HER2-negative breast cancer, improving survival outcomes. There are multiple CDK4/6 inhibitors available that differ in their pharmacologic features, reported outcomes, therapeutic indications, and adverse event profiles. Education is needed to empower clinicians to optimally use these agents in practice and personalize breast cancer treatment. The goal of this educational initiative was to increase the knowledge, competence, and confidence of oncologists regarding clinical trial data and factors for selection of CDK4/6 inhibitor. Methods: This educational approach included a 30-minute online video discussion among 3 expert faculty, synchronized with slides to support the discussion. Educational effectiveness was assessed with repeated paired pre/post assessment in which learners served as their own controls. A chi-square test assessed differences from pre- to post-assessment. P values &lt; .05 are statistically significant. Effect size was calculated using Cramer’s V test by determining the strength of the association between CME and the outcomes (V = .16-.26 is considerable and V &gt; .26 is extensive). The activity launched 11/25/2019 and data are reported through 2/4/2020. Results: A total of 889 learners, including 513 physician learners, participated in the activity from 11/2019 through 2/2020. Participation in the education resulted in significant improvements in knowledge among oncologists (n = 81; p &lt; .001; V = 0.16). On average, the proportion of learners who responded correctly to knowledge-based questions about CDK4/6 inhibitors increased from 51% at the pre-assessment to 67% at the post-assessment. Moreover, 41% of oncologists had a measurable positive change in confidence in their ability to incorporate CDK4/6 inhibitors into the treatment of HR+, HER2- advanced breast cancer. Significant improvements in knowledge were observed in the following areas: The clinical trial safety and efficacy data evaluating CDK4/6 inhibitors in the management of patients with HR+/HER2-negative breast cancer (32% vs. 51%, p &lt; .05, V = 0.19). The potential role of patient- and tumor- specific prognostic factors in selection of individual CDK4/6 inhibitors (56% vs. 72%, p &lt; .05, V = 0.17). Conclusions: This CME-certified online discussion resulted in statistically significant gains in oncologists’ knowledge and improved confidence surrounding the personalization of CDK4/6 inhibitor therapy in HR+/HER2- breast cancer.
Genome-wide association study on genetic variations associated with treatment failure after intravesical bacillus Calmette–Guérin therapy for non-muscle invasive bladder cancer.
Authors: Masaki Shiota, Naohiro Fujimoto, Yoshiaki Yamamoto, Ario Takeuchi, Katsunori Tatsugami, Takeshi Uchiumi, Hideyasu Matsuyama, Masatoshi Eto
Journal: Journal of Clinical Oncology (2020)

e17000 Background: Bacillus Calmette–Guérin (BCG) instillation is a key therapy to manage non-muscle invasive bladder cancer (NMIBC). However, intravesical BCG therapy fails in approximately half of patients, leading to recurrence and progression. We aimed to reveal the genetic variations associated with treatment failure after intravesical BCG therapy for NMIBC. Methods: This study included 91 Japanese patients treated with BCG instillation for NMIBC. Genomic DNA was obtained from patient whole blood samples, and a genome-wide association study and genotyping for target regions were performed. The association between genetic variation and treatment failure was analyzed by genome-wide association in 44 patients as the discovery cohort. As a validation study, candidate single nucleotide polymorphisms (SNPs) were examined among 47 patients in the distinct cohort. Results: The genome-wide association study indicated 19 candidate SNPs associated with BCG failure. Consistent results were obtained in six of these SNPs in the validation cohort. Following the combinational use of validated SNPs, 2-gene (rs73520681 and rs61094339) and 4-gene (rs4250, rs11894207, rs73520681, and rs61094339) models successfully predicted treatment failure after intravesical BCG therapy. Conclusions: This study showed that several SNPs were associated with outcome after intravesical BCG therapy in a Japanese population with NMIBC. The combinational use of these SNPs may have value in clinical applications, although this should be confirmed in future studies.
Heterozygous germline ATM mutations in breast cancer: A single academic center experience.
Authors: Anish S Konde, Kristina Ivan, Jeannie Klavanian, Tara Rangarajan, Ishmael A. Jaiyesimi, Dana Zakalik
Journal: Journal of Clinical Oncology (2020)

1537 Background: Heterozygous germline ATM mutation carriers have an increased risk of developing breast, pancreas, and other cancers. The clinical and pathologic characteristics of ATM-associated breast cancers have not been well defined. Methods: Patients who underwent multigene panel testing (MGPT) between 2013-2019 and identified to harbor ATM mutations were included in the study. We evaluated demographics, pathology, and surgical management of our ATM mutation carriers with breast cancer. Results: At total of 319 individuals were identified to have variants in ATM, of which 114 were pathogenic/likely pathogenic. The majority of patients were female (82%) and Caucasian (88%). A total of 56 patients (49%) had a personal cancer diagnosis, the most common of which was breast cancer (n = 39). Nine individuals had more than one primary malignancy. The mean age at breast cancer diagnosis was 52, with a range of 25-82. The majority of patients had invasive ductal carcinoma (74%), grade 2 or 3 (90%), and ER and /or PR positive (87%). Of those with known HER2 status, 24% were positive. Thirty-nine percent of patients were lymph node positive, and 42% had lymphovascular invasion. The most common stage at diagnosis was 2 (53%). Of the 39 mutation carriers with breast cancer, 16 (42%) received radiation therapy, and 16 underwent bilateral mastectomy. Of 114 ATM positive patients, there were 55 distinct variants. Sixteen (14%) individuals had a mutation in additional cancer predisposition genes. One variant, c.5015delG, was identified in ten patients in a large, consanguineous Iraqi family with an extensive history of pancreatic and other cancers. Eight individuals were identified to have the known high-penetrance variant, c.7271T &gt; G. Conclusions: Our study describes the clinical and pathological characteristics of ATM mutations carriers with breast cancer. The majority of patients had intermediate to high grade disease, hormone receptor positive, with a suggestion of a higher rate of HER2 positivity and lymph node involvement. Additional studies are needed to elucidate the unique characteristics of ATM-associated breast cancer, which may have implications for personalized management.
Comprehensive profiling of MDM2/TP53 genomic aberration in Chinese patients with diverse malignancies.
Authors: Dongkai Zhou, Weilin Wang, Sheng Yan, Song Ye, Yingsheng Wu, Yuan Ding, Qiang Sun, Xiaohui Qian, Bingqiang Gao, Yang Kong, Qifan Yang, Weiping Ji, Zhihai Zheng, Xiumin Zhou, Weihua Xu, Mingjin She, Yong Yang, Qiantong Dong, Yaojun Yu, Shiyue Zhang
Journal: Journal of Clinical Oncology (2020)

e13508 Background: Murine double minute-2 (MDM2) has increasing clinic relevance as preclinical and early clinical evidences have showed that the MDM2 inhibitors are promising alternative treatments for patients with MDM2-amplified (-amp) and TP53-wild-type (-WT) tumors by preventing TP53 protein degradation. However, exploration into genomic landscape of MDM2/TP53 across various solid tumors in Chinese patients is still limited. Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor samples were collected from 10010 Chinese patients with solid tumors and subjected to a clinical-grade next-generation sequencing (NGS)-based 450 gene panel testing carried out by a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Genomic alterations (GAs) including single base substitutions, short and long insertion/deletions (Indels), copy number variations, gene fusions, and rearrangements were analyzed. Tumor mutational burden (TMB) was measured by a NGS algorithm. Results: Amplification of MDM2 occurred in 3.3% of Chinese patients. MDM2-amp was detected most frequently in soft tissue sarcoma (STS, 11.4 %), melanoma (10.3 %) and osteosarcoma (6.3 %). Notably, MDM2-amp was revealed to be mutually exclusive with TP53-mut in most tumor types other than esophageal carcinoma (93.9 %), head and neck carcinoma (68.4%) and ovarian carcinoma (50 %). Tumors with highest frequencies of MDM2-amp/ TP53-WT were melanoma (100%), osteosarcoma (100%) and urothelial carcinoma (100 %). The most common co-altered genes accompanied with MDM2-amp were FRS2 (84%), CDK4 (38%), EGFR (26%), TP53 (17%) and GLI1 (14%). 82.8% patients who had one or more co-alterations potentially targetable with either FDA-approved or investigational agent. Moreover, TMB of MDM2-amp tumors were significantly lower than that of MDM2-WT and MDM2-mutation (-mut) tumors (median TMB: 3.1 vs. 4.6 vs. 10.8, p &lt; 0.001 respectively). Conclusions: MDM2 amplification was found in 3.3% of 10010 Chinese cancer patients, 83.4% of whom harbored wild-type TP53 that were potentially responsive to MDM2 inhibitors. In addition, 82.8% of the patients with MDM2-amp harbored genomic co-alterations and were potentially therapy targetable. This study provided insights into identifying patients who might potentially benefit from anti-MDM2 therapies.