tbuckley/cabot-search huggingface dataset:
Low-cost oral metronomic versus intravenous chemotherapy in recurrent, inoperable and metastatic head and neck cancer: Phase III Metro-CIS study.
Authors: Nandini Sharrel Menon, Vanita Noronha, Vijay Maruti Patil, Sachin Babanrao Dhumal, Amit Joshi, Nilesh Sable, Suman Kumar, Abhishek Mahajan, Atanu Bhattacharjee, Shripad Dinanath Banavali, Kumar Prabhash
Journal: Journal of Clinical Oncology (2020)

6506 Background: The NCCN preferred regimens for palliation in head and neck cancer, either EXTREME or KEYNOTE-048 are the only two regimens which have improved outcomes over chemotherapy, but they have limited applicability (1-3%) in low and middle-income countries due to the cost. Oral metronomic chemotherapy (OMC) has shown better outcomes than intravenous cisplatin; these results were obtained with a low incidence of adverse events and the cost of 1/100th of NCCN-preferred regimens in a Phase II study. Methods: This was a randomized Phase III non-inferiority open-label study. Adult patients with relapsed-recurrent or metastatic upfront palliatively treated squamous cell carcinoma of head and neck and ECOG PS 0-1 were eligible. Patients were randomized 1:1 between OMC (oral methotrexate 15 mg/m 2 weekly with celecoxib 200 mg once daily or intravenous cisplatin (IVC) 75 mg/m 2 , 3-weekly for 6 cycles. CTCAE version 4.0 was used for adverse event recording. Response assessment (RECIST version 1.1) was performed every 2 months. EORTC QLQ-C 30 and EORTC QLQ -H&amp;N 35 questionnaires were self-administered at baseline and 2-monthly thereafter. The primary endpoint was overall survival (OS) and was measured from the date of randomization to death. Assuming a 6-month OS in IVC arm of 40%, the non-inferiority margin of 13%, type 1 error of 5% (2-sided), type 2 error of 20% and lost-to-follow up rate of 20%, a total sample size of 422 subjects was required. Kaplan Meier method was used for the estimation of OS and progression-free survival (PFS). To determine non-inferiority the upper limit of 95% CI of difference between 6 months OS of the 2 arms had to be below 13%. Results: In the intention to treat analysis, the 6-months OS was 50.89% (95% CI, 43.3-57.97) and 62.26% (95% CI, 54.72-68.9) in the IVC and OMC arm respectively. The difference in 6-months OS between the 2 arms was - 11.37% (95% CI, -20.77 to -0.97). The median OS was 6.1 (95% CI, 5.33-6.93) versus 7.5 (95% CI, 6.5-8.8) months in IVC arm and OMC arm respectively ( P= .026). The unadjusted hazard ratio for death was 0.773 (95% CI, 0.615-0.97, P= .026). The median PFS was 1.67 (95% CI, 1.47-2.03) versus 3.23 (95% CI, 2.57-4.13) months in IVC and OMC arms respectively ( P&lt; 0.001). Any grade 3 or above adverse events were seen in 61 (30.2%) versus 37 (18.9%) patients in IVC and OMC arm respectively ( P= .01). Conclusions: OMC improves outcomes in palliatively treated head and neck cancer and is a new standard of care in this setting, in addition to the EXTREME and KEYNOTE-048 regimen. Clinical trial information: CTRI/2015/11/006388 .
Real-world incidence of grade III/IV side effects, emergency room visits, and hospital admissions after treatment with adjuvant durvalumab in locally advanced non-small cell lung cancer.
Authors: Syed Imran Mustafa Jafri, Nerea Lopetegui-Lia, Aswanth Reddy, James Vredenburgh
Journal: Journal of Clinical Oncology (2020)

e19276 Background: Durvalumab is a selective human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80, allowing T cells to recognize and kill tumor cells. Durvalumab is FDA approved for adjuvant treatment of locally advanced unresectable NSCLC after definitive chemoradiation based on data presented in the PACIFIC trial with benefit in PFS and overall survival. In the PACIFIC trial, discontinuation of the durvalumab because of adverse events occurred in 15.4% of the patients. The most frequent adverse events leading to its discontinuation were pneumonitis (4.8%), radiation pneumonitis (1.3%), and pneumonia (1.1%). The aim of our study is to review real world single institution experience of durvalumab in locally advanced NSCLC. Methods: 23 patient charts with locally advanced NSCLC who had durvalumab ordered for adjuvant treatment were reviewed. 4 patients were excluded given failure to start durvalumab or lack of complete records with treatment at outside institutions. Results: 19 patients were included in the final analysis. 18/19 patients received definitive chemoRT and 1 patient received definitive RT alone given co-morbidities. 8 patients finished durvalumab and 4 are currently on treatment. 8/19 patients (42.1%) had Grade III/IV side effects reported. 7/19 (36.8%) patients had durvalumab discontinued. In 6 patients (31.5%), durvalumab was discontinued due to Grade III/IV toxicity (all with pneumonitis) while 1 patient had sepsis with disease progression. 2 patient had died with one patient death related to pneumonitis/pneumonia along with underlying co-morbidities and the second patient with disease progression. 4 patients (21%) had 7 ER visits and 5 patients (26%) were admitted to the hospital for various reasons 7 times. 2 patients required higher level of care in the step down unit. Treatment was delayed only twice in all 19 patients because of a clinical reason. Conclusions: Durvalumab is an exciting new development in the treatment of locally advanced NSCLC. Our review revealed higher than previously reported incidence of pulmonary toxicity as well as higher discontinuation rate. Other than pulmonary toxicity, durvalumab is very well tolerated with low incidence of ER visits, hospital admissions and treatment delays. Clinicians should monitor patients very closely for pulmonary toxicity during durvalumab treatment. Regular pulmonary function testing may be a reasonable approach to monitor the patients on durvalumab.
Outcomes of Lynch syndrome (LS) patients treated with immune checkpoint inhibitors (ICI).
Authors: Shahla Bari, Richard D. Kim, Xia Wang, Marco Matejcic, Jameel Muzaffar
Journal: Journal of Clinical Oncology (2020)

1548 Background: LS is caused by a germline mutation in one of several DNA mismatch repair (MMR) genes: MLH1, MSH2, MSH6 or PMS2 (d-MMR). A minority of LS patients have MMR proficient tumors (p-MMR). ICI therapy has dramatically changed outcome of d-MMR (majority of LS patients. However, data about response to ICI in LS patients, irrespective of their tumor MMR status is scarce. The aim of this study was to evaluate outcomes of ICI therapy in all LS associated Cancer. Methods: This was a retrospective analysis of LS associated cancers treated with one of the 6 ICIs at our center. We also looked at age, sex, microsatellite status, response and survival. Results: Out of 262 LS patients analyzed, 194 had cancer and 22 received ICIs. Among the patients analyzed, the mean age at diagnosis of 1 st cancer was 51 yrs. There were 10 females (47%). 10 patients had colorectal (45%), 3 urothelial (14%), 2 renal cell, 2 cholangiocarcinoma and one each of esophageal, ovarian, uterine, glioblastoma multiforme and pancreatic cancer. One patient died from progressive disease after receiving a single dose and was not included in the analysis. 17 patients (80%) received Pembrolizumab, 11 patients were microsatellite unstable (MSI), 3 were microsatellite stable (MSS) while 7 were unknown. 2 patients achieved complete response (CR) (10%), 1 patient had partial response (PR) (5%), 13 had stable disease (62%) while 5 had progressive disease (23%) leading to a disease control rate (DCR) of 76%. Of the 3 known MSS Lynch syndrome patients, 2 did not respond while the 3 rd continues to respond at 9 months of therapy. Of the 5 patients who had PD, 2 were MSS, 2 unknown and 1 MSI. Among the 16 patients who responded, 15 of 16 (94%) had sustained response and have not experienced disease progression or relapse. 3 of these patients have been off therapy (1 due to immune related adverse evet) and have had no relapse. One responder progressed after 18 cycles of therapy. The DCR was 71% at 12 months as well as 48 months of follow up. Median progression survival has not been reached. Similarly, median overall survival has not been reached. Conclusions: Our study is the one of the largest reported analysis of LS associated cancer patients treated with ICIs and included LS patients with both MSI and MSS tumors. Though small, our data suggests robust DCR and prolonged responses in Lynch associated MSS tumors treated with ICI. This encouraging response in MSS tumors along with higher response rates in LS associated cancers as compared to non-LS MSI tumors, suggests that there may be additional drivers of response to ICI in LS patients leading to superior responses.
Derivation of a machine learning model to predict clinical outcome in patients with primary biliary cholangitis
Authors: Jorn Goet, Surain Roberts, Gideon Hirschfield, Pietro Invernizzi, Marco Carbone, Palak Trivedi, Christophe Corpechot, Harry La Janssen, Rozanne de Veer, Willem J Lammers, Marlyn J Mayo, Pier M Battezzati, Annarosa Floreani, Albert Pares, Frederik Nevens, Andrew L Mason, Kris Kowdley, Cyriel Ponsioen, Tony Bruns, George N Dalekos, Douglas Thorburn, Xavier Verhelst, Keith D Lindor, Adriaan J Van der Meer, Niels D Goet, Bettina E Hansen, Henk R Van Buuren
Journal: Hepatology (2019)
The predictive values of mutation patterns, concurrent mutations and efficacy of different generations of EGFR-TKIs in advanced non-small cell lung cancer harboring non-resistant uncommon EGFR mutations.
Authors: Pengbo Deng, Jiarong Tan, Chengping Hu, Liming Cao, Huaping Yang, Min Li, Qihua Gu, Yuanyuan Li, Jian An, Han Han-Zhang
Journal: Journal of Clinical Oncology (2020)

e21612 Background: The efficacy of EGFR-TKIs in patients with non-resistant uncommon EGFR mutations is controversial. The predictive values of mutation patterns, the presence of concurrent mutations and the choice of different generations of EGFR-TKI have not been well elucidated. Methods: We retrospectively enrolled 190 NSCLC patients with non-resistant uncommon EGFR mutations, defined as mutations other than single L858R, 19del, T790M or 20ins. Among them, 72 were advanced/recurrent patients who received 1st (N = 55) or 2nd generation (N = 17) EGFR-TKIs as first-line therapy and with retrievable PFS data; therefore, were enrolled for subsequent survival analyses. Results: Patients were categorized according mutation patterns: group1 patients harboring EGFR uncommon mutation in combination with EGFR 19 del/L858R; group 2 patients harboring single or complex EGFR uncommon mutations. Our analyses revealed that the median PFS (mPFS) of group 1 was significantly longer than those in groups 2 (14.65months vs 8.05 months; P = 0.004). Next, we investigated whether the presence of concurrent mutations in tumor suppressor genes or oncogenes would affect PFS. The mPFS of patients with no concurrent mutation, patients with concurrent tumor-suppressor genes mutations and patients with concurrent oncogenic driver mutations were 13.57m, 8.05m and 16.92m, respectively (p = 0.04). Patients with no concurrent mutation had a significantly longer mPFS than patients with concurrent tumor-suppressor genes mutations (p = 0.013). Collectively, multivariate analysis revealed that patients receiving 2nd generation TKI (p = 0.006, HR:0.277,95%CI:0.112-0.688) and coexist with 19del/L858R (p &lt; 0.001, HR: 0.148,95% CI:0.065-0.333) were independently associated with favorable PFS; while concurrent TP53 mutation was independently associated with worse PFS (p = 0.008, HR: 2.530,95% CI:1.270-5.042). Conclusions: Our study revealed NSCLC patients harboring non-resistant uncommon EGFR mutations in combination with 19del/L858R were associated with favorable PFS. The presence of concurrent tumor-suppressor genes mutations especially TP53 is associated with worse prognosis. Patients treated with 2nd generation EGFR-TKI showed a longer PFS than those treated with 1st generation TKI.
改良泪道探通治疗新生儿泪囊炎90例
Authors: 李广涛, 孙鼎
Journal: BMJ (2005)

新生儿泪囊炎临床常见,亦称先天性泪囊炎,患儿出现溢泪,压迫泪囊区有脓性分泌物溢出或冲洗液自上泪道溢出,诊断容易.我院自1992年至2003年采用泪道冲洗加玻璃酸钠注入治疗新生儿泪囊炎收到较好效果。
Increase in side effect bother was associated with early treatment discontinuation in a clinical trial among multiple myeloma patients.
Authors: John Peipert, Fengmin Zhao, Ju-Whei Lee, Fangxin Hong, Edward Ip, Ilana F Gareen, Nathaniel O'Connell, Ruth Carlos, A. Keith Stewart, Matthias Weiss, Joseph A. Sparano, David Cella, Robert James Gray, Lynne I. Wagner
Journal: Journal of Clinical Oncology (2020)

e19136 Background: Patient reported side effect bother is needed to understand tolerability of cancer drugs. We examined whether increase in side effect bother from baseline to cycle 7 as measured by a single item (GP5) from the FACT-G, “I am bothered by side effects of treatment”, was associated with early treatment discontinuation (ETD) in a multiple myeloma (MM) trial. Methods: Data were drawn from the induction phase of ECOG ACRIN E1A06, a two arm, phase 3 trial conducted in patients with untreated MM. The induction phase occurred over twelve, 28-day cycles. GP5 was assessed at registration and cycle 7. ETD was defined as completion of less than 12 cycles of treatment. We tested whether increase in side effect bother on the GP5 from baseline to cycle 7 was associated with months to ETD in two ways. At each timepoint, GP5 was rated with these response options: “Not at all”, “A little bit”, “Somewhat”, “Quite a bit”, “Very Much”. First, we stratified Kaplan Meier curves by patients with versus without substantially increased side effect burden from registration to cycle 7 on the GP5, defined as an increase of &gt; 2 response categories; Cox regression was used to calculate a hazard ratio. Second, we fit a joint model of the GP5 change trajectory on months to ETD that substituted the estimated slope of a longitudinal logistic regression model into the hazard function of a Cox model. In this model, GP5 was dichotomized as 0 = “Not at all/”A little bit”; 1 = “Somewhat”/ “Quite a bit”/ “Very Much”. Results: 159 patients were followed during induction for a median of 11 months (range: 0.2-16.0). 10 patients (6%) reported a substantial increase on GP5 from registration to cycle 7. After 16 months, these patients had a significantly higher hazard of ETD as estimated by Kaplan Meier methods: 40% experienced ETD vs. 24% of patients without substantial GP5 increase [hazard ratio (HR): 3.08 (95% CI: 1.18-8.02)]. In the joint model, the effect of GP5 on hazard of ETD was larger [HR: 9.56 (95% CI: 2.41-37.82)]. Conclusions: This study found initial evidence that increase in side effect bother as measured by the GP5 predicts ETD and may therefore reflect treatment intolerability in cancer drug trials. The effects found in this study will be tested for replication in additional ECOG-ACRIN trials with diverse designs, treatments, and cancer types. Clinical trial information: NCT00602641 .
Perceptions of US Adolescents and Adults With Sickle Cell Disease on Their Quality of Care
Authors: Julie Kanter, Robert Gibson, Raymona H. Lawrence, Matthew P. Smeltzer, Norma L. Pugh, Jeffrey Glassberg, Rita V. Masese, Allison A. King, Cecelia Calhoun, Jane S. Hankins, Marsha Treadwell
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Sickle cell disease (SCD) is the most common inherited red blood cell disorder in the United States, and previous studies have shown that individuals with SCD are affected by multiple health disparities, including stigmatization, inequities in funding, and worse health outcomes, which may preclude their ability to access quality health care. This needs assessment was performed as part of the Sickle Cell Disease Implementation Consortium (SCDIC) to assess barriers to care that may be faced by individuals with SCD. <h3>Objective</h3> To assess the SCD-related medical care experience of adolescents and adults with SCD. <h3>Design, Setting, and Participants</h3> This one-time survey study evaluated pain interference, quality of health care, and self-efficacy of 440 adults and adolescents (aged 15 to 50 years) with SCD of all genotypes and assessed how these variables were associated with their perceptions of outpatient and emergency department (ED) care. The surveys were administered once during office visits by trained study coordinators at 7 of 8 SCDIC sites in 2018. <h3>Results</h3> The SCDIC sites did not report the number of individuals approached to participate in this study; thus, a response rate could not be calculated. In addition, respondents were not required to answer every question in the survey; thus, the response rate per question differed for each variable. Of 440 individuals with SCD, participants were primarily female (245 [55.7%]) and African American (428 [97.3%]) individuals, with a mean (SD) age of 27.8 (8.6) years. The majority of participants (306 of 435 [70.3%]) had hemoglobin SS or hemoglobin S β<sup>0</sup>-thalassemia. Most respondents (361 of 437 [82.6%]) reported access to nonacute (usual) SCD care, and the majority of respondents (382 of 413 [92.1%]) noted satisfaction with their usual care physician. Of 435 participants, 287 (66.0%) reported requiring an ED visit for acute pain in the previous year. Respondents were less pleased with their ED care than their usual care clinician, with approximately half (146 of 287 [50.9%]) being satisfied with or perceiving having adequate quality care in the ED. Participants also noted that when they experienced severe pain or clinician lack of empathy, this was associated with a negative quality of care. Age group was associated with ED satisfaction, with younger patients (&lt;19 vs 19-30 and 31-50 years) reporting better ED experiences. <h3>Conclusions and Relevance</h3> These results suggested that a negative perception of care may be a barrier for patients seeking care. These findings underscore the necessity of implementation studies to improve access to quality care for this population, especially in the acute care setting.
聚维酮碘消毒致眼表损害诊治分析
Authors: 胡小坤, 庄鹏, 林映竑, 韩雅玲
Journal: BMJ (2011)

聚维酮碘( povidone-iodine,PVP-Ⅰ)具有广谱的抗微生物作用,最初是作为外科医生手部及患者术前皮肤的消毒广泛应用于临床.PVP-Ⅰ的乙醇溶液作为医生手术前手的消毒[1],是非常有效的手术野皮肤消毒剂[2],但若不慎落入眼内,会对眼表产生损害.现将我院2008年6月至2010年12月眼科会诊的13例PVP-Ⅰ致眼表损害诊治情况报告如下. 关键词：眼损伤
Return of results after somatic tumor mutation profiling in advanced cancer: Psychological impacts.
Authors: Phyllis Butow, Grace Davies, Christine Napier, David Morgan Thomas, Nicole Bartley, David Goldstein, Mandy L. Ballinger, Ilona Juraskova, Timothy E Schlub, Kathy Tucker, Bettina Meiser, Mary-Anne Young
Journal: Journal of Clinical Oncology (2020)

1541 Background: Somatic tumor mutation profiling (STMP) is entering clinical practice. We aimed to investigate psychological impacts of receiving results. Methods: Eligible participants had: advanced solid cancers of any histological type; accessible tissue for STMP; and enrolled in the Molecular Screening and Therapeutics (MoST) Program. 1074 participants (91%) completed a baseline assessment prior to STMP (T0), of whom 570 (47%) received results and completed a post-result assessment (T1) of impact of genetic results (MICRA), anxiety and depression (HADS), cancer-specific anxiety (IES), and satisfaction with decision to have STMP. Linear regression models controlling for age, gender, parental status, cultural diversity, education and ECOG status explored associations between result received and psychological outcomes. Results: 360 participants received an actionable result and were recommended personalised treatment: 152 via a MoST sub-study (G1) and 208 via their treating oncologist (G2). 210 received a non-actionable result (G3). At T1, G3 were significantly more distressed and less positive about their result (MICRA subscales) and less satisfied with their decision to have STMP than both G1 and G2; G2 was less positive than G1. IES and HADs were not impacted by type of result. Interactions between gender and age, and result were non-significant for all psychological outcomes. Perceived self-efficacy in coping with results (p=0.015) and knowledge (p=0.04) at T0 was significantly correlated with satisfaction with decision at T1; self efficacy (T0) was also correlated with MICRA total (T1) (p=0.006). Conclusions: Pathway to treatment receipt is less important to advanced cancer patients than actionability. Patients’ self-efficacy to cope with results prior to testing can identify patients vulnerable to distress post-receipt of STMP results who should be offered psychological counseling. Ensuring good knowledge of STMP at consent may avoid decisional regret. [Table: see text]
Outcomes and the impact of genomic characteristics on patients with metastatic urothelial carcinoma enrolled in early phase trials.
Authors: Omar Alhalabi, Andrew W Hahn, Funda Meric-Bernstam, Aung Naing, Sarina Anne Piha-Paul, Filip Janku, Shubham Pant, Timothy A Yap, David S. Hong, Siqing Fu, Erick Campbell, Hung Le, Amishi Yogesh Shah, Matthew T Campbell, Nizar M. Tannir, Arlene O. Siefker-Radtke, Jianjun Gao, Jason Roszik, Vivek Subbiah
Journal: Journal of Clinical Oncology (2020)

5029 Background: With the recent approvals of checkpoint inhibitors (CPIs), a fibroblast growth factor receptor (FGFR) inhibitor, and an antibody-drug conjugate, patients with platinum-refractory metastatic urothelial carcinoma (mUC) have several treatment options available. However, many patients with platinum-refractory mUC need novel therapies after progressing on current therapies. We assessed the role of early phase trials in treatment of mUC and the impact of genomic alterations on their outcomes. Methods: We retrospectively analyzed medical records of patients with mUC who received an investigational therapy at the phase 1 clinic and had CLIA-certified clinical next generation sequencing. Clinical parameters and mutations were abstracted. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier methods. Hazard ratios (HR) were calculated using the Cox proportional hazard model. Results: Among the 57 pts enrolled in 41 unique phase 1 trials between 2015 and 2019, 16% (9/57) had variant histology: neuroendocrine carcinoma (n = 3) and urachal carcinoma (n = 6). Median age was 64. Majority were males (72%). 97% received prior platinum therapy and 60% had received prior CPI therapy. Across the pure urothelial carcinoma cohort (n = 48), median PFS was 4.2 months (m), median OS was 9.8 m, and the overall response rate (ORR) was 19%. TP53, FGFR, TERT, and ARID1A alterations (alt) were detected in 54%, 41%, 21% and 17% of UC patients, respectively. Patients harboring a TP53 alt, compared to no alt, had a shorter median PFS of 3.2m vs 9.6 m (HR = 2.738 [1.247 - 6.011], p = 0.0121). On the contrary, median PFS was longer in FGFR alt, compared to no alt, 6.3m vs 3.2m (HR = 0.4662 [0.224 - 0.971], p = 0.0415). Of note, 64% of FGFR alt patients were treated under an early phase FGFR targeting trial. Median OS was numerically longer in FGFR alt and shorter in TP53 alt but did not reach statistical significance (table). Conclusions: Patients with mUC may derive clinical benefit from enrollment in phase I clinical trials. Patients with TP53 alterations had numerically worse outcomes. Patients with mUC should be considered for an FGFR targeting therapy in the setting of an FGFR alteration. [Table: see text]
创伤性膈疝手术的麻醉体会
Authors: 张玉荣, 杨川, 张有才, 权大荣
Journal: BMJ (2011)

创伤性膈疝是由外伤导致膈肌破裂,腹腔内容物进入胸腔,不同程度地压迫心肺而致的一系列改变,重者引起呼吸循环功能障碍,乃至休克,危及生命.创伤性膈疝一经确诊或高度怀疑,应立即手术,及时修补膈肌缺口.但此类患者伤情复杂,生理功能紊乱严重,手术过程中给麻醉带来一定难度.现对我院1993年至2009年间收治的12例创伤性膈疝修补术的麻醉处理经验总结如下。