tbuckley/cabot-search huggingface dataset:
Minimizing drug wastage (DW) and cost of cabazitaxel used to treat metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Di Maria Jiang, Nazanin Fallah-Rad, Roy Lee, Pamela Ng, Alan D. Smith, Aaron Richard Hansen, Anthony M. Joshua, Srikala S. Sridhar
Journal: Journal of Clinical Oncology (2019)

6550 Background: Cabazitaxel is indicated for mCRPC, but is associated with substantial DW and financial strain on hospital budgets. It is only available in single-dose 60mg vials and has short reconstituted drug stability of &lt; 24 hours. We aimed to determine feasibility and cost savings of an aggressive batching strategy to facilitate vial sharing of Cabazitaxel. Methods: Our mitigation strategy was to administer Cabazitaxel 20mg/m 2 q3-weekly (without prophylactic G-CSF) on a single weekday whenever possible. Drug was prepared after patient (pt) arrival. Remaining amount from each vial was saved for subsequent pts on the same day. Amount administered, discarded and number of (#) vials used were obtained from pharmacy records. We estimated drug cost without batching by assigning 1 vial/treatment, and drug cost with batching from the actual # vials used. Cost of DW was determined from the amount discarded. All cost calculations were based on market price ($96.7CAD/mg) accounting for Sanofi’s discount incentive (5 vials for the price of 4), allowing a real-world cost assessment. Results: Between 09/2015 and 09/2018, 74 pts received 404 Cabazitaxel treatments on 164 days using 319 vials. Multiple pts were batched on 68% treatment days. Every 3 pts batched saved 1 vial. Average dose/treatment was 37mg (20-45mg). Among 10 treatment cancellations, prepared drug was administered for subsequent pts in 9 cases. Drug and DW costs over the 3-year period with and without batching are shown in Table. Conclusions: Batching ≥3 pts on a single weekday was feasible and significantly lowered drug cost of Cabazitaxel by reducing wastage. This strategy could help mitigate costs associated with wastage for other oncology drugs. [Table: see text]
Prognostic implications of lymph node metastasis in advanced ovarian cancer: Analysis of the National Cancer Database 2006 to 2014.
Authors: Mohamed Elgamal, Sukamal Saha, Meghan Cherry, Vishesh Saharan, Robin Buttar, David Wiese, Neelum Dutt, Trevor Singh, David S. Eilender, Sandeep Singh Grewal, Madan L. Arora
Journal: Journal of Clinical Oncology (2019)

e17042 Background: During debulking surgery (Surg) for advanced ovarian cancer (OvCa), lymph node (LN) sampling is not routinely performed. Hence, prognostic implications of LN involvement following debulking surg and chemotherapy (ChemoRx) were analyzed from the National Cancer Database (NCDB). Methods: Only Stage III and IV patients (pts) from NCDB 2006–2014 undergoing debulking surg and ChemoRx were included. Group A: pts with debulking surg without bowel resection; Group B: pts with major bowel resection and Group C: pts with bowel and bladder resection. Pts were further subdivided according to the use of 1) NeoAdjuvant (NeoAdj) 2) Adjuvant (Adj) and 3) NeoAdj and Adj ChemoRx. Survival analysis was done based on -ve or +ve LN status. Pearson Chi Square testing was used to evaluate the survival between -ve and +ve LN pts. Results: A total of 13839 Pts were included. There were 5757 Pts (41.59%) with -ve LN status, versus 8082 Pts (68.4%) with +ve LN status. Out of 10,737 Stage III and 3,102 Stage IV pts, there were 6,828 in Group A, 6,413 in Group B and 598 in Group C pts. For all patients in Groups A, B, and C, the 5 yr overall survival was better in LN -ve than LN +ve pts. The overall survival for both LN -ve and LN +ve pts was better in Adjuvant chemoRx in all 3 groups, except for Stage III Group C LN-ve pts, where NeoAdj was better (75% vs 37.5%). Overall survival was also slightly better in Stage III vs Stage IV pts. (Table-1). Conclusions: Even though LN dissection is not routinely done during debulking surgery, overall pts with LN metastasis do worse than LN -ve pts irrespective of the timing of ChemoRx. Hence, LN sampling during debulking surg should be strongly considered, as it may provide important prognostic information. Table-1: 5 yr Survival by LN status [Table: see text]
Clinical prognostic factors in patients with recurrent or metastatic carcinoma of the head and neck treated with immune checkpoints therapies.
Authors: Carlo Resteghini, Stefano Cavalieri, Alessandro Rametta, Salvatore Alfieri, Donata Galbiati, Francesca Platini, Laura Deborah Locati, Paolo Bossi, Cristiana Bergamini, Roberta Granata, Ester Orlandi, Cesare Piazza, Moela Mancinelli, Lisa F. Licitra
Journal: Journal of Clinical Oncology (2019)

e17530 Background: Immunotherapy (IT) provides advantages in a small proportion of recurrent / metastatic head and neck squamous cell carcinoma (RM HNSCC) patients (pts). Predictive biomarkers are still an unmet need. We aimed to determine if known prognostic clinical factors in RM HNSCC as well as new variables hold prognostic value in the IT era. Methods: We conducted a retrospective analysis of a cohort of 106 RM HNSCC pts enrolled into IT trials at National Cancer Institute of Milan-Italy between Oct 2014 - Jul 2018. Using Log Rank test and Cox proportional hazard model we computed univariate and multivariate analysis (UVA; MVA) of demographics, clinical and biological data to assess their prognostic value for progression free survival (PFS) and overall survival (OS). Results: Ninety-three pts (M 75; F: 18) were included in the final analysis with a median follow up of 20.8 months. The majority (96%) were treated in platinum-refractory setting. Approximately half of pts received anti-PD-1 or anti-PDL-1 monotherapy while the remaining 52% received them in combination with other IT agents. Median OS and PFS were 6.5 (CI 95%: 4.6-10.4) and 2.1 months (CI 95%: 1.8-2.2), respectively. Statistically significant factors at UVA for PFS were smoking history - both pos vs neg and &lt; vs ≥ 30 PY, disease subsite, weight loss &gt; 5%, Karnosfky performance status (PSK), occurrence of any and G3-G4 drug related (DR) toxicities, neutrophil to lymphocytes ratio (NLR). Without stratification for disease subsite, MVA showed independent predictive value of prolonged PFS for positive smoking history (HR 0.5, p 0.02) and any DR toxicities (HR 0.43, p &lt; 0.01). Several factors reached significance for OS in UVA (smoking history and PY, weight loss &gt; 5%, ECOG PS, PSK, occurrence of any toxicities, CRP, baseline C-reactive protein, antibiotic use, steroid use in the 30 days before IT). Of these, PSK (HR 0.95, p 0.01) and any DR toxicities (HR 0.3, p &lt; 0.01) resulted to be predictive in the MVA. Conclusions: Clinical parameters, especially pretreatment PSK, smoking history and occurrence of any DR toxicities, appear to be strong predictors of outcome in RM HNSCC pts treated with IT. These results should be validated in an independent cohort.
Functional profile and clinical significance of major tumor infiltrating lymphocyte subsets in lung cancer-associated brain metastases.
Authors: Benjamin Y. Lu, Richa Gupta, Tyler Stewart, Harriet M. Kluger, Lucia Jilaveanu, Kurt A. Schalper, Sarah B. Goldberg
Journal: Journal of Clinical Oncology (2019)

2066 Background: Despite the biological and clinical implications, the immune composition and functional characteristics of adaptive immune cells in brain metastases (BrM) are poorly understood. Using multiplexed quantitative immunofluorescence (QIF), this study evaluates the level and functional profile of major T-cell subsets in primary lung tumors, BrM, and extracranial metastases (ECM) from lung cancers. Methods: A tissue microarray was constructed from formalin-fixed, paraffin-embedded tumor samples of 94 lung cancer patients treated at Yale Cancer Center between 2002-2013. Multiplexed QIF was used to evaluate the cases with a panel containing phenotype markers for major T-cell subsets (CD3, CD4, CD8 and FOXP3), and cell-localized activation and proliferation (granzyme-B and Ki-67). Signal for each marker was measured in marker-selected tissue compartments using the Automated Quantitative Analysis (AQUA) platform. Associations between markers and major clinicopathologic variables were studied. Results: In total, 40 primary lung tumors, 63 BrM, and 15 ECM were analyzed, including paired samples from 22 patients. Lung cancer histology included adenocarcinoma 62.5%, squamous cell carcinoma 11.5%, small cell 9.4%, and other non-small cell 16.7%. BrM had both significantly lower levels of CD3+ T-cells ( p&lt; 0.0001) and T-cell granzyme B ( p= 0.0188) compared with primary lung tumors. No significant differences were observed in T-cell Ki-67 levels across tissues. FOXP3 measured in CD4+ T-cells were significantly lower in BrM compared with primary malignancies ( p= 0.0002) and ECM ( p= 0.0404). Among patients with BrM, higher levels of CD3+ T-cells in BrM were associated with longer overall survival. Conclusions: Lung cancer-associated BrM have lower T-cell infiltration, cytolytic function, and regulatory T-cells than primary lesions. These results indicate lower adaptive anti-tumor responses in BrM and suggest the presence of a tolerogenic microenvironment in the brain. Overcoming this could be used to design optimal treatment strategies.
Mutation profiles in circulating tumor DNA (ctDNA) to predict the efficacy of sorafenib treatment in patients with advanced hepatocellular carcinoma (HCC).
Authors: Ping Yang, Guanghui Ji, Qionghui Jiang, Zejun Lu, Yao Yu, Yadong Yang, Ge Jin
Journal: Journal of Clinical Oncology (2019)

e15648 Background: To find biomarkers from blood samples through ctDNA and leucocyte genomic DNA sequencing to predict the efficacy of sorafenib. Methods: CtDNA and leucocyte genomic DNA were extracted from patients with advanced hepatocellular carcinoma for sequencing analysis before and after targeted therapy with sorafenib. Mutation profiles were obtained by deep sequencing of 620 selected genes for further bioinformatics analysis. Gene mutation frequency and status were further integrated with clinical data to dynamically monitor and predict the efficacy of sorafenib. Results: Twelve patients with advanced hepatocellular carcinoma admitted to our hospital from March 2017 to September 2018 were enrolled. A total of 27 blood samples were collected for further analysis. The results showed that there were significant differences in BRD4 and FANCG gene mutation abundance between therapeutic effect group and poor effect group (p = 0.014). The mutations of BRD4, FANCG and TP53 were associated with shorter PFS (BRD4 mutation type vs wild type: 12 weeks vs 32 weeks, p = 0.0011; FANCG mutation type vs wild type: 16 weeks vs 32 weeks, p = 0.0103; TP53 mutation type vs wild type: 8 weeks vs 32 weeks, p = 0.0095). Furthermore, we found another 19 genes (SDHA, OTUD7A, TMPRSS2, NAV3, AKT1, EIF2S2, DICER1, MAP3K1, RAD9A, TCF3, IRS1, PIK3C2G, CTCF, TSHZ2, ITPKB, KDM5C, STAG2, AMER1, CDC27) associated with therapeutic efficacy, and dynamic changes of these 19 genes mutation alleys could predict therapeutic efficacy. Conclusions: Our results showed that mutations in ctDNA could predict the efficacy and prognosis of sorafenib for advanced hepatocellular carcinoma, and that dynamic monitoring of mutation frequency in ctDNA of peripheral blood samples could be an additional method to monitor therapeutic efficacy of sorafenib. The clinical significance of the mutations of BRD4, FANCG, TP53 and another 19 genes we found needs to be confirmed on a larger scale.
Understanding cancer care coordination: Opening the black box.
Authors: Maureen Canavan, Tannaz Sedghi, Cary Philip Gross, Stacey Lane, Jeanette Bogdan, Kerin B. Adelson
Journal: Journal of Clinical Oncology (2019)

e18310 Background: Cancer care is complex, requiring multidisciplinary care over time and settings. Our implementation strategy for participation in CMS’ Oncology Care Model included the development of a new care management program to provide elderly patients with cancer support and continuity between inpatient and outpatient care with the goal of reducing acute care utilization. With no published models of care coordination in cancer, we launched this program using nurses experience to risk stratify and manage the needs of nearly 2500 patients. To optimize their work, we sought to understand the activity breakdown of their working time and to identify areas that can be managed more efficiently. Methods: Care coordinators are nurses responsible for completing the Institute of Medicine (IOM) care plan, stratifying patients by risk and comorbidity and administering weekly symptom assessment scales to those at high risk for disease and treatment complications. We created, pilot tested and refined a data collection tool that care coordinators could self-report the time they spent in activities of direct and indirect patient care. We performed a desk audit to measure the amount of time that oncology care coordinators spend on various activities and to explore differences in academic center versus care center care coordinators. A total of seven care coordinators self-reported activity specific time for 5 working days. Data were analyzed to assess variation in the proportion of activity time by care coordinator, site of care and day of the week using anova and t-test for the difference in mean activity time. Results: Care coordinators spent the majority of their time in indirect patient care (58%) with the highest percentage of their time specifically on charting/documentation (28%) while only 42% of their time included activities that were direct patient care. We observed no significant difference in the proportion of time spent in direct versus indirect patient care across care coordinators (p = 0.47, day of the week (p = 0.35) or by location of care (p = 0.68). Conclusions: A minority of care coordinators time is spent on providing direct patient care and substantial time is spent on indirect activities including charting and documentation. The efficiency of the care coordination model may be improved by transferring tasks that do not require the clinical expertise of these nurses.
Sex-Based Differences in Heart Failure Across the Ejection Fraction Spectrum
Authors: Davide Stolfo, Alicia Uijl, Ola Vedin, Anna Strömberg, Ulrika Ljung Faxén, Giuseppe M C Rosano, Gianfranco Sinagra, Ulf Dahlström, Gianluigi Savarese
Journal: JACC Heart Failure (2019)
Highly Stable Core–Shell Structured Semiconducting Polymer Nanoparticles for FRET‐Based Intracellular pH Imaging
Authors: Biqing Bao, Peng Su, Zhenyuan Yang, Xue Zhai, Jingjing Zhang, Yu Xu, Yunfei Liu, Bingbing Gu, Lianhui Wang
Journal: Advanced Healthcare Materials (2019)

Abstract Highly stable semiconducting polymer nanoparticles (NPs) (poly(9,9‐dioctylfluorenyl‐2,7‐diyl) (PFO)/ poly(fluorene‐2,7‐ylenevinylene‐ co ‐phenylene) (PFV)‐dopamine (DA) NPs) with previously unreported core–shell structure are developed for ratiometric sensing of intracellular pH values. PFO/PFV‐DA NPs comprise central polyfluorene (PFO) as donor and PFV as acceptor, in which the donor and acceptor are spatially separated into the central core and nanoparticle shell. Specifically, thick PFV shells can not only significantly minimize the quenching interference of dopamine on the emission of standard reference (PFO), but are also able to maximize its accessibility to pH‐sensitive dopamine and lead to sensitive response to pH changes. The resulting core–shell PFO/PFV NPs are structurally and optically stable, which can avoid the photobleaching and leakage of materials issues compared to traditional semiconducting polymer nanoparticles (SPNs)‐based fluorescence resonance energy transfer (FRET) systems containing small molecules. Additionally, the designed compact PFO/PFV‐DA NPs show quantitative response to the pH values in aqueous media and are capable of mapping intracellular pH fluctuations by ratiometric imaging. This work may open up opportunities for the generalizability of the consistent ratiometric emission intensity strategy based on core–shell structured SPNs nanoprobes for highly sensitive biological sensing.
Correlation of systemic and local inflammation with survival prognosis in glioma patients.
Authors: Pegah Mir Seyed Nazari, Cihan Ay, Christine Marosi, Florian Moik, Julia Riedl, Gerda Ricken, Johannes A. Hainfellner, Matthias Preusser, Ingrid Pabinger, Anna Sophie Berghoff
Journal: Journal of Clinical Oncology (2019)

2052 Background: Immune modulating therapies have been a long withstanding treatment approach in glioma. However, gliomas are characterized by a particular absence of tumor infiltrating lymphocytes in the local tumor microenvironment. We aimed to gain insight on the distinct patterns of inflammation associated with survival prognosis in glioma. Methods: Patients were recruited at time of glioma diagnosis or progression in the prospective observational Vienna Cancer and Thrombosis Study (CATS). A single blood draw was performed at study inclusion. PD-L1 expression in the tumor tissue was investigated via immunohistochemistry. Optimal cut-off according to ROC curve was used to assess cut off values for survival analysis. Results: 193 patients with glioma (75.6% glioblastoma (WHO grade IV), 19.7% anaplastic glioma (WHO grade III), and 4.7% diffuse glioma (WHO grade II)) were included. 40/193 (20.7%) glioma had an IDH1 mutation. Membranous PDL1 expression in the tumor tissue was observed in 20/193 (10.4%) patients. 1/20 patient presented with PD-L1 expression and IDH1 mutation ( p = 0.082). PD-L1 significantly correlated with increased monocyte count (median: 0.657 vs. 0.450 [G/L], p = 0.008), higher C-reactive protein (CRP) (0.43 vs. 0.1 [mg/dL], p = 0.005) and higher fibrinogen (379 vs. 303 [mg/dL], p = 0.001). Presence of IDH1 mutation significantly correlated with increased platelet count (303 vs. 232 [G/L], p = 0.001) and lower Neutrophil/Lymphocyte (N/L) ratio (3.34 vs. 5.13, p = 0.016). Higher lymphocyte count ( &gt; 1.484 [G/L], log-rank: p = 0.011), higher platelet count ( &gt; 245.5 [G/L], p = 0.0001), as well as decreased N/L ratio ( &lt; 5.13, p = 0.001) were significantly associated with increased survival prognosis. Conclusions: PD-L1 expression in tumor tissue was associated with markers of systemic inflammation in glioma patients. Systemic inflammation markers furthermore predicted improved survival. Immune modulating therapy approaches might be a promising approach in subgroups of glioma associated with increased baseline interaction of immune system and glioma.
RNA-based biomarker signatures in plasma as an independent predictor of outcome to chemotherapy in lung, colon, and breast cancers: Correlation of relative PD-L1 expression with immunotherapy outcomes.
Authors: Luis E. Raez, Joshua L. Usher, KATHLEEN DANENBERG, Daniel Sumarriva, Aurelio Bartolome Castrellon, Shahrooz Rabizadeh, Adriana Milillo, Brian Hunis, Sandip Reddy, Liyang Huang, Jennifer Zikria, Pablo Ferraro, Peter Danenberg
Journal: Journal of Clinical Oncology (2019)

e14567 Background: Levels of cell-free circulating RNA (cfRNA) in cancer patients (pts) indicate tumor gene expressions and thus may provide a means, not only of evaluating response, but also for monitoring and predicting outcome to therapy. Methods: Blood was drawn every 6-8 weeks from pts undergoing various treatments (tx). CfRNA was extracted from resulting plasma and generated random-primed cDNA. Total cfRNA was quantitated by qPCR of β-actin, and correlated with pts response (CR/PR/SD/PD) determined by CT scans. Changes in PD-L1 expression were used to monitor response to immunotherapy in lung cancer pts. 125 pts (50 lung, 51 breast, 24 colon) were enrolled. Among the three tumor types, a total of 84 pts completed 1-3 lines of tx with an average of 5 blood draws per pt. Results: Changes in total levels of cfRNA over time correlated with pts outcomes in all three tumor types and were independent of the specific therapies. Increasing (INC) levels of cfRNA were predictive of disease progression and decreasing (DEC) levels with benefit from therapy, with an overall concordance of 81% (68/84 pts). Changes in relative PD-L1 expression were associated with immunotherapy outcomes in lung cancer (INC associated with progression, DEC associated with benefit). Lung: There was a 79% (23/29) concordance between changes in cfRNA levels and pts response. Changes in relative PD-L1 expression were predictive of outcome to immunotherapy in 9/10 pts. Breast: There was an 83% (30/36) concordance between cfRNA levels and pts response. Colon: There was a 79% (15/19) concordance between cfRNA levels and pts response. Conclusions: A noteworthy concordance was observed between clinical response and changes in cfRNA levels in lung, breast and colon cancer pts, independent of chemotherapy regimen. Changes in relative PD-L1 gene expression correlated specifically with outcome to immunotherapy (90%). We conclude that changing cfRNA levels can indicate tx response, and PD- L1 could be used to monitor response to immunotherapy.
Serial ctDNA analysis as a real-time indicator of neoadjuvant chemoradiotherapy in rectal cancer.
Authors: Jiaolin Zhou, Guole Lin, Yuhua Gong, Yanyan Zhang, Yan-Fang Guan, Xuefeng Xia, Xin Yi, Xiaoqiang Xue, Xueshan Bai, Ling Yang
Journal: Journal of Clinical Oncology (2019)

3569 Background: Neoadjuvant chemoradiotherapy (nCRT) is nowadays the standard of care for the locally advanced rectal cancer (LARC). However, there is no effective method to predict patients’ possible benefits from nCRT and monitor the response to it. Methods: Patients with locally advanced middle and low rectal cancer of stage cT3-4N0M0 or cTanyN+M0 were enrolled from August 2017 to July 2018. All patients received nCRT with long-term radiation plus fluorouracil based chemotherapy, followed by the radical surgery. Serial plasma samples were collected pre-nCRT, during nCRT, and preoperatively (8 weeks after the completion of nCRT). Somatic mutations were detected with next-generation sequencing using a 1021-gene panel with peripheral blood lymphocyte DNA as a germline control. Results: This prospective cohort study enrolled 61 patients with rectal cancer. The pathological complete response (pCR) rate and the downstage rate was 31% (19/61) and 80% (49/61), respectively. ctDNA was detectable in 77% (47/61), 18% (11/61) and 13% (8/61) of blood samples obtained pre-nCRT, during nCRT and preoperatively, respectively. No significant association was observed between pre-nCRT ctDNA status with any clinicopathological factors, including age, gender, differentiation or tumor circumferential extent. Among the 8 patients with detectable ctDNA preoperatively, pathological tumor regression grade (TRG) of CAP 2-3 were observed and hepatic metastasis was found in 4 patients within 2 months. For patients with undetectable pre-operative ctDNA, a higher proportion archived pathological downstaging (85% vs 50%). The correlation between preoperative ctDNA status and achievement of pathological downstage was independent of age, gender or differentiation (p = 0.02). In addition, preoperative ctDNA positivity was associated with the persistently involved lymph node (p = 0.02). However, neither pre-nCRT nor during-nCRT ctDNA status was associated with pathological downstaging or persistently lymph node involvement. Conclusions: Detectable ctDNA after the completion of nCRT is a predicator of unsatisfactory curative effect of patients with LARC, which might indicate novel treatment intensification studies. Clinical trial information: NCT03042000.