tbuckley/cabot-search huggingface dataset:
Analysis of chemotherapy-related modulation of the immune microenvironment in muscle invasive bladder cancer.
Authors: Elshad Hasanov, William Tabayoyong, Jianfeng Chen, Guoliang Yang, Fengqi Nie, Jieru Meng, Anh Hoang, Yueting Zhu, Eleni Efstathiou, Jolan Bondaruk, Wei-Lien Wang, Charles Guo, Miao Zhang, Bogdan Czerniak, Christopher Logothetis, Ashish M. Kamat, Jianjun Gao
Journal: Journal of Clinical Oncology (2020)

5049 Background: Novel immune checkpoint inhibitors provide significant clinical benefits for patients with metastatic bladder cancer. It is known that chemotherapy administered to muscle invasive patients prior to radical cystectomy (neoadjuvant chemotherapy) improves survival. However, it is unknown whether immune checkpoint inhibitor therapy in combination with chemotherapy can provide further clinical benefits as neoadjuvant therapy. Here, we test the hypothesis that treatment of bladder cancer with certain chemotherapy agents can modulate bladder tumor immune microenvironment (TIME) for optimal combination with immune checkpoint therapy. Methods: Time course and dose response experiments were performed using eight human bladder cancer cell lines (UMUC3, RT4, 253J, RT112, J82, HT1376, T24, and HT1197) and two murine bladder cancer cell lines (MB49, MBT2). Conventional chemotherapy agents and combinations (MVAC, GemCis, PemVin) were used to treat bladder cancer cell lines. Flow cytometry analysis was used to measure immune cell subsets and PD-L1 expression. For in vivo studies, the subcutaneous MB49 murine bladder cancer model was used to evaluate responses to chemotherapy and anti-PD-L1 combinations. Pre- and post-treatment bladder tumors from patients who received neoadjuvant MVAC and GemCis are selected to evaluate changes in TIME. Results: Our data demonstrate that chemotherapy agents varies in their ability to up-regulate PD-L1 expression on bladder cancer cell lines. Vinblastine, gemcitabine, and pemetrexed treatment each resulted in significant upregulation of PD-L1 expression. Combination regimens with GemCis or PemVin demonstrated induction of PD-L1 across different cell lines. In in-vivo studies, GemCis + anti-PD-L1 had a synergistic activity in causing tumor regression. We also found that sequential versus concurrent treatment with chemotherapy and anti-PD-L1 had a similar outcome. Tissue analyses show that combination chemotherapies increased CD4 Th cell infiltration while decreasing Treg cells in TIME. Consistent with the in vitro data, PD-L1 expression was also up-regulated with combination treatment. The evaluation of TIME modulation in human bladder tumors treated with neoadjuvant MVAC or GemCis is ongoing. Conclusions: Our data suggest that chemotherapy could favorably modulate TIME and thus, may be combined with immune checkpoint inhibitor to improve anti-tumor responses in the neoadjuvant setting for patients with muscle invasive bladder cancer.
Dashboard directed decision support to increase cancer survivorship care plan adherence.
Authors: Yazan Rizeq, Casey Brackett, Rawan Yousef, Ferdynand Hebal, Susan Budds, Ruta D. Rao, Mia Alyce Levy
Journal: Journal of Clinical Oncology (2020)

e24043 Background: Oncology practices face multiple challenges when trying to implement the Commission on Cancer (CoC) Survivorship Care Plan (SCP) documentation standard. First, it is difficult to systematically identify patients who qualify for a SCP from the electronic medical record (EMR). Second, SCP documentation must be completed within a specific timeframe that does not always align with clinical encounters for routine care. Finally, as practices participate in more regulatory programs, such as the Oncology Care Model (OCM), the burden of meeting the unique but often overlapping documentation standards becomes burdensome. Our goal was to improve adherence to SCP documentation through enhanced clinical documentation workflows and clinical decision support. Methods: To meet CoC SCP standards, SCP templates were built into the EPIC EMR at a single multi-centered institution. These templates allowed the user to indicate on the problem list if the SCP was needed. Likewise, Institute of Medicine (IOM) care plan documentation templates and reminders were built to meet OCM standards. Population dashboards were developed in Tableau to track SCP documentation adherence and provide support regarding eligible patients who required SCP documentation. Patients were eligible who had a cancer diagnosis codes on the problem list, and MC in the EMR. Patients greater than 12 months from being marked curative were considered eligible to complete SCP. Results: Between 2015-2019, 2763 cancer patients were MC by 31 providers, where 806 (30%) were OCM patients. Overall, 1372 (70%) non-OCM patients required an SCP, where 563 (41%) were completed. When examining the OCM patients, 689 (85%) required a SCP, where 552 (80%) were completed. For patients MC in 2018, 163/439 (37%) and 137/190 (72%) of patients received a SCP for the non-OCM and OCM group respectively. For patient MC in 2019 after implementation of the decision support dashboard, 115/145 (79%) and 144/148 (97%) of eligible patients had completed SCP for the non-OCM and OCM group respectively (Table). Conclusions: During the study period, adherence to SCP documentation doubled concordant with CoC standards at that time. Integration of IOM and SCP documentation improved adherence among OMC compared to non-OCM patients. The decision support dashboard helped prioritize cases for SCP documentation for care teams. This is an example of a decision support framework that could be used for other standards driven documentation requirements in cancer.
Neoadjuvant chemoradiation (CRT) for locally advanced rectal cancer (LARC) with or without oxaliplatin (OX): Individual patient data (IPD) meta-analysis of three randomized controlled trials (RCTs) with subgroup analyses of age cohorts.
Authors: Elisa Fontana, Clizia Zichi, Elizabeth Catherine Smyth, Murielle E. Mauer, Claus Roedel, Emmanouil Fokas, Ralf Dieter Hofheinz, Dirk Arnold, Hans-Joachim Schmoll, Eric Van Cutsem, Karin Haustermans, Alexander Stein, Jean-Pierre Gerard, Thierry Conroy, Claire Jouffroy-Zeller, Markus H. Moehler, Florian Lordick, Irit Ben-Aharon, Massimo Di Maio
Journal: Journal of Clinical Oncology (2020)

4074 Background: Neoadjuvant CRT with fluoropyrimidine (FP) is standard treatment for LARC, which is increasing in younger patients (pts). RCTs examining the addition of OX are still controversial. A post hoc analysis of the CAO/ARO/AIO-04 trial showed significant benefit in pts &lt; 60y. We hypothesised that younger pts with LARC might have improved outcomes with OX-CRT. Methods: Systematic review and IPD meta-analysis were performed. Data from 3 RCTs (CAO/ARO/AIO-04, ACCORD-12, PETACC-6) testing the addition of OX to standard FP-based CRT in LARC were available (of 9 RCTs identified). Primary endpoint: disease-free survival (DFS), secondary endpoints: pathologic complete response (pCR), overall survival (OS). Analyses were by intention to treat (ITT), stratified by trial. Age cut-offs were 60y and 50y. Given the focus on young age a multivariate analysis evaluating all possible confounders was not intended in the current work. Results: IPD from 2914 pts were included (48.5% of available literature). Median age was 63; 70% were male; 79% had a performance status = 0; 72% were stage ≥III. In ITT (Hazard Ratio [HR] 0.88, 95%CI 0.77-1.01, p = 0.06), DFS was not significantly improved by the addition of OX (Table). In &lt; 60y (n = 1166, 40% total), DFS was significantly improved by OX (HR 0.77, 95%CI 0.62-0.96, p = 0.02). In &lt; 50y (n = 350, 12% total) there was a numerically better DFS, although not significant (HR 0.73, 95%CI 0.49-1.08, p = 0.12). Interaction test between age and DFS was non-significant (60y p = 0.11; 50y p = 0.44). In ITT, OX increased pCR from 13% to 16% (Odds Ratio [OR] 1.28, 95%CI 1.04-1.57, p = 0.024 [stratified by trial]), without significant interaction with age (60y p = 0.11, 50y p = 0.74). No OS benefit was demonstrated (HR 0.97, 95%CI 0.82-1.15, p = 0.75). Conclusions: This first IPD meta-analysis of three RCTs evaluating the addition of OX to CRT did not show significant interaction of OX with age. However, we confirm a signal for DFS benefit in pts &lt; 60y and a non-significant increment in DFS in &lt; 50 y although this analysis may be underpowered. Stage-stratified analyses and feasibility/toxicity data in age cohorts will be presented. [Table: see text]
Reliability and validity of Chinese version NASA-TLX and SWAT in evaluating mental workload of community physicians
Authors: Man Li, Zhigang Pan, Jie Gu
Journal: BMJ (2015)

Objective
To assess the reliability and validity of Chinese version National Aeronautics and Space Administration Task Load Index (NASA-TLX) and Subjective Work Assessment Technique (SWAT) in evaluating mental workload of community physicians.


Methods
One hundred and ten community physicians selected by convenience sampling method from Shanghai were recruited. The split-half reliability, Cronbach's α coefficient and Item-total coefficients were adopted to assess the reliability and the validity of Chinese version NASA-TLX and SWAT scales in evaluating the metal workload of participants.


Results
For NASA-TLX, the Split-Half, Cronbach's α coefficient was 0.703 and 0.619 respectively, all Item-total coefficients (except for performance item) were greater than 0.4 (P<0.01). For SWAT, the Split-Half, Cronbach's α coefficient of was 0.647 and 0.669 respectively, Item-total coefficients were all greater than 0.4 (P<0.01). Factor analysis showed that two scales had good structure validity; item discrimination showed satisfactory item validity (except for performance item). The Spearman correlation coefficients between two scales ranged from 0.359 to 0.465 (P<0.01). Both of the modified versions of NASA-TLX had better reliability and validity than the original one, the one with removed both performance and frustrate item was better than one with removed performance item only.


Conclusions
The Chinese version NASA-TLX and SWAT can serve as reliable and valid instruments for assessing the community physicians' perception of mental workload in China; and the modified version of NASA-TLX especially the one with removed performance and frustrate item seems to work better than the original one.


Key words: 
Evaluation studies; Mental workload; Community physician
Patterns in detection of recurrence among patients treated for breast cancer.
Authors: Lena Saltbæk, Trine Allerslev Horsbøll, Birgitte Vrou Offersen, Michael Andersson, Anne Sofie Friberg, Signe Korsgaard Skriver, Pernille Bidstrup, Jens Overgaard, Christoffer Johansen, Susanne Oksbjerg Dalton
Journal: Journal of Clinical Oncology (2020)

e14020 Background: Follow-up programs for breast cancer should according to ASCO and ESMO consist of regular visits including anamnestic screening for symptoms of recurrence and physical examination for ten years in addition to regular mammography. Recently, the Danish guideline for follow-up after early breast cancer was revised. Today most patients are offered open access to an outpatient clinic, but no scheduled visits following the first year after surgery. This strategy has been studied in regards to psychological and health related quality of life outcomes, but not in regards to detection of recurrence and survival. The aim of this study was to quantify the recurrences detected at scheduled outpatient visits in Denmark before the implementation of revised follow-up guidelines. Furthermore, we aimed to assess whether the duration of symptoms prior to recurrence detection differed depending on type of visit when recurrence was detected. Methods: We conducted a cross-sectional study among 310 patients with recurrent breast cancer. Through medical records, we retrieved information on type of visit when recurrence was detected, localization of recurrence, symptoms reported, and duration of symptoms. Tumor characteristics were obtained from the Danish Breast Cancer Group database. Results: Among the 310 breast cancer recurrences, more than half were distant (59%), 26% were loco-regional, and 15% loco-regional and distant. Among the 199 patients still in outpatient follow-up at time of recurrence, recurrence was detected at a scheduled outpatient visit (21%), at a patient-requested extra outpatient visit (15%), by the general practitioner or other specialist (47%), or on a scheduled mammography (11%). Among patients with recurrence detected at a scheduled outpatient visit, the majority (88%) reported symptoms related to the recurrence. Patients who waited for the scheduled outpatient visit despite symptoms had a markedly longer duration of symptoms (median 21 weeks) prior to detection of recurrence than patients who requested an extra visit (median 8 weeks). Conclusions: One-fifth of recurrences among patients attending outpatient follow-up were detected at scheduled outpatient visits. The majority was symptomatic, but the patients had not altered their scheduled appointment. Whether recurrences like these will be detected in follow-up without scheduled visits is unknown. Some recurrences may be detected earlier, if patients can be educated to react on relevant symptoms, but some recurrences may be detected with further delay. Thus, more research in this area is needed.
Post-operative delirium in older patients following cancer related and other high-risk surgeries.
Authors: Rawad Elias, Ilene Staff, Stephen Thompson, Christine Waszynski, Jennifer Zanchi, Robert Dicks
Journal: Journal of Clinical Oncology (2020)

e24024 Background: Older adults are at increased risk for postoperative delirium (POD). This risk might be higher in patients with cancer as underlying malignancy and its complications predispose individuals to develop delirium. Therefore, it is important to evaluate the onset of delirium in this patient population especially as POD is associated with increased risk of rehospitalization, decline in cognitive function, morbidity and mortality. Methods: We performed a retrospective review of patients aged ≥ 70 years admitted January 2017 through July 2019 to a tertiary care referral center for a high-risk surgery, defined as associated with a mortality risk greater than 1%. Cancer related surgeries (CRS) were identified through cross matching with Cancer Registry. Patients who had delirium assessment in the postoperative setting using the Confusion Assessment Method (CAM) were included. Chi-square tests of proportion, Wilcoxon Ranked Sum and multivariate logistic regression analyses were conducted. Results: A total of 2340 patients were included in this analysis, 315 of whom had (CRS). Overall, the age (median, IQR) of patients at surgery was 76 years (72-80) and the length of stay (LOS) was 7 (4-11) days. Patients receiving CRS were younger (75, 72-79) than those with non-CRS (76, 72-81) (p = 0.022); had a shorter post-operative LOS (4, 2-7 vs. 5, 3-8; p &gt; 0.001), and were less likely to develop POD (7.6% vs. 16.1%; p &lt; 0.001). Among patients receiving CSR, those who developed POD were older (78 vs. 74; p = 0.008) and had longer post-operative LOS (14.0 vs. 4.0; p &lt; 0.001). Those having experienced radiotherapy (RT) for cancer within the year before the surgery, were more likely to develop POD (40.0% vs. 6.6% p. &lt; 0.001). Chemotherapy in the year prior to surgery did not increase the risk of POD (6.1% vs. 7.8%; p = 0.721). Among those having non-CRS, a cancer diagnosis did not affect POD. A logistic regression predicting POD indicated that the lower likelihood of POD following CRS was independent of age or gender (OR = 0.40; p &lt; .001); RT within one year prior was independent predictor of higher POD (OR = 5.48; p = 0.003). Our data presentation will include further analysis of POD risk factors. Conclusions: Although older adults receiving CRS were significantly less likely to develop delirium than patients with other high-risk surgeries, it is still important to evaluate POD in this population due to its impact of patients’ outcomes. Further understanding of POD risk factors, such as preoperative RT, would allow the development of targeted interventions that might lessen the risk.
Predicting the efficacy of nivolumab combined with radiation therapy by longitudinal liquid biopsy with artificial intelligence for patients with metastatic breast cancer (translational research of the KBCRN-B-002 trial).
Authors: Kosuke Kawaguchi, Masahiro Takada, Takeshi Kotake, Michio Yoshimura, Ryuji Uozumi, Masako Kataoka, Takahiko Koyama, Reitaro Tokumasu, Hironori Kato, Hiroshi Yoshibayashi, Hirofumi Suwa, Wakako Tsuji, Hiroyasu Yamashiro, Tatsuki R Kataoka, Hiroshi Ishiguro, Laxmi Parida, Satoshi Morita, Masakazu Toi
Journal: Journal of Clinical Oncology (2020)

e15046 Background: Advances in immuno-oncology (IO), i.e., programmed cell-death protein 1 (PD-1) inhibitors, are revolutionizing cancer treatment by offering hope for a cure. However, the benefit of IO agents in metastatic breast cancer (MBC) remains limited. For immunotherapy to be successful, it is essential to understand the tumor immune contexture. Systemic immune alterations, such as the signature of peripheral blood mononuclear cells (PBMC) and cytokine expression, are one of the hallmarks of successful immunotherapy in MBC. The abscopal effect induced by radiation therapy (RT) is known to be a modulator of systemic immune alterations, and the abscopal effect is considered as a systemic anti-tumor immune response. In this study, we integrated time series multi-omics data in order to identify alteration of the immune signatures after RT combined with nivolumab, a PD-1 inhibitor, using a longitudinal liquid biopsy with artificial intelligence. Methods: This study was conducted as translational research, part of the KBCRN-B-002 trial, which is a multicenter phase Ib/II study evaluating the safety and efficacy of nivolumab in combination with RT in patients with HER2-negative MBC (UMIN: UMIN000026046). Twenty-nine patients were included in the translational analysis set. The multi-omics data included data from RNAseq, mass cytometry (CyTOF) and multiple cytokines, using PBMC, serum and plasma. We collected time series data, which covered the baseline, two weeks after starting therapy, four weeks after starting therapy and the timing of progressive disease. For integrated analysis of the multi-omics data, a machine-learning method was developed. Results: Our integrated analysis (involving a longitudinal liquid biopsy and machine-learning method) identified an apparent cluster of responder groups and alteration of the systemic immune signatures. Single-cell analysis using CyTOF results including the signature of the immune cell composition, effector immune cells and immune suppressor cells. Conclusions: Our method clustered responders well and identified candidates of the systemic immune signatures for actionable hallmarks of RT combined with IO agent by a longitudinal liquid biopsy. Clinical trial information: NCT03430479 .
Phase I/II study of R-ICE (rituximab-ifosfamide-carboplatin-etoposide) with lenalidomide (R2-ICE) in patients with first-relapse/primary refractory diffuse large B-cell lymphoma (DLBCL) in academic and community cancer research united (ACCRU) network.
Authors: Francis Guerra-Bauman, Betsy LaPlant, William R. Macon, Thomas E. Witzig, Umar Farooq, Grzegorz S. Nowakowski, Tatyana Feldman
Journal: Journal of Clinical Oncology (2020)

TPS8073 Background: Response rates to salvage immunochemotherapy in patients with DLBCL relapsing after or refractory (R/R DLBCL) to front line therapy remain unsatisfactory. Lenalidomide (Len) has significant single agent activity in relapsed/refractory DLBCL. The addition of lenalidomide (Len) days 1-7 to rituximab plus ifosfamide-carboplatin-etoposide (RICE) was shown to be feasible with promising efficacy in phase 1b study (Feldman T, et al. BJH, 2014). We developed phase I/II study to evaluate the safety and efficacy of the addition of Len (extended to 14 day schedule) to RICE (R2-ICE) for R/R-DLBCL patients who are candidates for stem cell transplant. Methods: The phase I portion was designed to determine the maximally tolerated dose Len in combination with RICE using the standard cohort 3+3 design. The escalation dose levels were 15 mg and 20 mg daily x 14 days. Prophylactic aspirin and growth factor support is mandatory. After 2 cycles of therapy response is evaluated with a PET/CT scan; the responding patients are eligible for 1-2 additional cycles of R2ICE as a bridging before HDC/SCT. The estimated overall response rate for two cycles of R-ICE in R/R DLBCL to RCHOP was estimated to be approximate 45%. We hypothesize that the addition of lenalidomide in the relapse setting could increase the overall response rate by approximately 20%. The one-stage design with an interim analysis being utilized in phase 2 requires 45 evaluable patients (one sided alpha = 0.09, power 90%). For Phase I, all types of B-cell lymphomas were eligible. For phase II portion only DLBCL patients are eligible per central pathology review. Other eligibility criteria include: received one line of previous anti-lymphoma therapy, ≥ 2 weeks from completion of prior anti-lymphoma therapy, candidate for HDC and SCT, adequate organ (creatinine clearance ≥ 60ml/min by Cockcroft-, total bilirubin ≤ 2 × ULN) and bone marrow function (ANC) ≥1500/mm 3 ; platelet count ≥75,000/mm3). The use of steroids and/or rituximab up to 1 week prior to registration for management of symptoms is allowed. 9 patients cleared phase 1 without DLT and dose of 20 mg days 1 -14 was recommend for phase 2 part (RP2D) of the study. The phase 2 study passed interim futility analysis and accrual continues. Correlatives include cell of origin by Nanostring, Myc/bcl2 expression and by FISH and minimal residual disease. PET scans are centrally reviewed including metabolic tumor volume. Clinical trial information: NCT02628405 .
Clinical analysis of tracheobronchial foreign bodies combined with atelectasis in children
Authors: Hui Zhang, Weixi Zhang, Haijie Xiang, Ruru Chen, Changchong Li
Journal: BMJ (2017)

Clinical data of 62 cases of tracheobronchial foreign bodies with pulmonary atelectasis admitted in Second Affiliated Hospital and Yuying Children′s Hospital during January 2007 to December 2016 were retrospectively analyzed. There were 40 boys and 22 girls aged 9 months to 10 years, and the symptom onset ranged from 6 hours to 4 months prior to medical intervention. The foreign bodies were vegetables in 55 (88.71%), pieces of meat in 3 (4.84%) and chemical product in 4 cases (6.45%). Sixty patients recovered after medical intervention, 1 died preoperatively and 1 died of severe reexpansion pulmonary edema (RPE). The foreign bodies were successfully removed with rigid bronchoscopy in a single attempt in 47 children (77.05%), 1 child (1.64%) required two attempts to completely remove the foreign bodies; 10 children (16.39%) were treated with fiberoptic bronchoscopy; 3 children (4.92%) received thoracotomy, in which 1 child (1.64%) received a lobectomy due to pulmonary atelectasis and lung consolidation during operation.


Conclusion
Foreign bodies combined with pulmonary atelectasis in children are likely to be misdiagnosed, which led to severe adverse events. RPE is a serious postoperative complication of children receiving rigid bronchoscopy as a treatment, especially those diagnosed with tracheobronchial foreign bodies combined with pulmonary atelectasis.


Key words: 
Child; Foreign bodies; Pulmonary atelectasis; Bronchoscopy
妊娠合并原发性干燥综合征、抗磷脂综合征并发肺栓塞一例
Authors: 李玉苹, 叶民, 林锡芳, 陈成水, 陈少贤
Journal: BMJ (2007)

患者女,25岁,农民.因停经8个月余,右下肢肿胀伴疼痛半月,呼吸困难2 d,于2005年11月3日入我院重症监护病房(ICU).既往月经规律,末次月经2005年3月2日,孕期未进行产前检查.有口干、眼干病史2年,无关节痛、皮疹等。