tbuckley/cabot-search huggingface dataset:
Data collection for care pathways in the Cleveland Clinic Health System.
Authors: Katherine Glass, Chad W Cummings, Marc A. Shapiro, Dennis Urbanek, Brian James Bolwell
Journal: Journal of Clinical Oncology (2016)

115 Background: Care pathways are established methods of reducing healthcare costs and disparities in oncology care. To demonstrate their impact, health systems must measure and report data on care pathway adherence and outcomes in near real-time. Automating data abstraction across a health system for oncology is difficult due to the amount and detail of data required. Manual abstraction of data is considered slow and costly. Many consider Electronic Medical Record (EMR) integration of care pathways essential in order to successfully implement and assess. Methods: 7 medical oncology care pathways and 45 medical oncologists across the health system were selected for a pilot study to assess the feasibility of implementing care pathways throughout the enterprise. The pilot study also allowed for testing of data collection capabilities. Patients eligible for the care pathways were prospectively identified by manual review of physician calendars. A small number of data points were manually abstracted from the patient EMR at the time of identification. Endpoints of interest, such as hospitalization rates, chemotherapy administered, time to treatment, and costs of care were reconciled through pre-existing databases within pharmacy, research, and finance. Tumor registry data identified a retrospective cohort. Results: Over 1,000 patients were prospectively identified for the care pathway pilot between 1/1/2014 and 12/31/2014. The tumor registry identified 700 additional retrospective patients. The rapid analyses possible as a result of these efforts demonstrated physician adherence, improved patient outcomes, and significant cost savings. In one example, a care pathway for metastatic non-small cell lung cancer reduced charges by more than $98,000/patient by recommending patients receive one standardized chemotherapeutic regimen. Conclusions: Timely data collection for oncology care pathways is feasible and cost effective without EMR integration. Manual identification of patients combined with pre-existing data sources allowed for near-real time analysis of care pathways and provided valuable information about care pathway impact. Institutions can implement and assess care pathways with resources already available to them.
Diagnosis and semiquantification of osteonecrosis of the jaw by bone scan index on bone scintigraphy.
Authors: Hiroshi Yaegashi, Atsushi Mizokami, Satoru Watanabe, Kenichi Nakajima, Natsuyo Noguchi, Shuichi Kawashiri, Mikio Namiki
Journal: Journal of Clinical Oncology (2016)

e639 Background: Bone management is extremely important for maintaining QOL of prostate or renal cancer patients with bone metastasis. Physicians often administrate bone modifying agents (BMA), zoledronic acid or denosumab, to prevent skeletal-related event and bone pain for such patients. However, osteonecrosis of the jaw (ONJ) is one of sever adverse events of BMA (Medication-related ONJ; MRONJ). The early detection and follow-up of ONJ is extremely important issue. In order to achieve this issue, we utilized bone scintigraphy and a computer-aided diagnosis using a bone scan index (BSI). Methods: A total of 22 patients with either prostate cancer or renal cancer (27 lesions) diagnosed with MRONJ after treatment with BMA were investigated. Median age was 72.5 years (range 52-82 years). The primary disease was prostate cancer (81.8%), renal cancer (18.2%). Regarding the treatment, 86.4% of the patients were treated with bisphosphonate drugs, none in denosumab, and both in 13.6%, respectively. The median duration of medication was 33 months (range 7-70 months) by the time of MRONJ diagnosis. All patients underwent Tc-99m methylene diphosphonate bone scintigraphy. Bone uptake in the jaw was analyzed using BSI, which was calculated by BONENAVI (FUJIFILM RI Pharma, Japan; EXINIbone, EXINI Diagnostics, Sweden). Significant hot spots were manually selected according to both serial scintigraphic images and dental records, and the fraction of them to the entire skeleton was referred as BSI of the jaw (BSIJ). The level of BSIJ was evaluated in comparison with stage of ONJ and inflammation marker, C-reactive protein (CRP). Results: The median BSIJ of lesions was 0.14 (range 0.00-0.43) at the time of MRONJ diagnosis. If MRONJ is not treated appropriately, BSIJ tended to increase during treatment with BMA. When patients were classified according to their clinical stages of MRONJ, higher stage MRONJ lesions had significantly higher BSIJ (p &lt; 0.01). In addition, BSIJ was correlated with CRP. Conclusions: Evaluation of BSIJ using BONENAVI on bone scintigraphy was helpful for early detection and follow-up of MRONJ. Furthermore, increased BSIJ on bone scintigraphy were related to CRP and stage of ONJ.
Clinicopathologic significance of expression of nuclear factor kappa Β and vascular endothelial growth factor in gastric cancer patients.
Authors: Keon-Woo Park, Hyuk-Chan Kwon, Su-Jin KIm, Hyung-Sik Lee
Journal: Journal of Clinical Oncology (2013)

50 Background: Nuclear factor-κB (NF-κB) and vascular endothelial growth factor (VEGF) are involved in cell proliferation, invasion, angiogenesis and metastases. The principal objective of this study was to assess the prognostic significance of NF-κB and VEGF expression in gastric cancer Methods: The tumor tissues of 154 patients with gastric cancer, all of whom underwent potentially curative resection, were immunohistochemically evaluated using monoclonal antibodies against NF-κB and VEGF. Results: Positivity rates of NF-κB and VEGF were 44.2% and 39.6%, respectively. NF-κB expression in tumor tissues was correlated significantly with VEGF expression (p &lt; 0.001). VEGF expression was related to Lauren’s classification (p = 0.002), differentiation (p = 0.043), depth of invasion (p = 0.005), carcinoembryonic antigen (p = 0.032), and stage (p = 0.026). However, NF-κB expression was not related to any of these parameters. Univariate analysis demonstrated that NF-κB expression was significantly related with both 5-year disease free survival (65.2% vs. 46.4%, p = 0.007), and 5-year overall survival (60.0% vs. 42.5%, p = 0.014). Multivariate analysis verified that NF-κB was independently associated with disease free survival (hazard ratio: 2.082, p = 0.005), and overall survival (hazard ratio: 1.841, p = 0.008). However, VEGF did not appear to be related to adverse clinical outcome. Conclusions: NF-κB expression in tumor tissue is associated with poor survival in gastric cancer patients.
Study on external Chinese herbal medicine LC09 treating hand-foot skin reaction associated with the multitargeted kinase inhibitors.
Authors: Y. Lou, L. Jia
Journal: Journal of Clinical Oncology (2010)

e19534 Background: Multitargeted Kinase Inhibitors (MKIs) has shown benefit in cancer therapy. However, the most clinically significant and dose-limiting dermatologic toxicities, particularly Hand-Foot Skin Reaction (HFSR), can impact quality of life (QoL) and may lead to MKIs dose modification or interruption. We examined the use of compound Chinese herbal medicine LC09 (including Herba Geranii, etc.) external treatment for MKIs-associated HFSR. Methods: Eligible patients(pts) with HFSR grade≥1 (NCI-CTCAE version 3.0), after sorafenib or sunitinib therapy. LC09 granules 10g was dissolved in 1,000mL of water (keep 20°C-25°C in a footbath), and pts soaked their feet and hands in the lotion for 20 minutes, twice daily for 7 days. Pts were assessed before and after treatment, including a physical examination. Evaluation criteria, CR as symptoms disappear completely, PR as grade for HFSR decreases more than 1 level, Total response rate as CR+PR. The QoL of pts were also assessed by Skindex-16 (a dermatologic QoL patient reported questionnaire). Results: 12 pts have been enrolled, all of them are Asian, 11 male and 1 female. The associated cancer was HCC in 7 cases, RCC in 4 and NSCLC for 1. The median age was 62.5 yrs (range 56-102), Grade1 HFSR was seen in 1 pts, G2 in 1, G3 in 10. Total response rate was 91.7%(11/12), CR 25.0%(3/12), PR 66.7%(8/12). The average time from therapy beginning to pain relieves was 1.3±1.1 days. The skin lesion of HFSR including blisters, peeling, ulceration have been improved after treatment. The mean score of the QoL before and after treatment were 49.25±14.45 and 12.08±13.06 (out of a total of 96, p<0.001). The most significant complaint was pain, the mean score were 4.08±1.55 and 0.75 ±1.36 (on a scale of 0–6, p<0.001). No side effect such as allergy or infection related to LC09 was found. Conclusions: Compound external Chinese herbal medicine LC09 can treat MKIs-associated HFSR, which is especially effective for relieving pain and helpful for the skin lesion, easy use and safe. Thus improve the QoL of pts with HFSR after sorafenib or sunitinib therapy. No significant financial relationships to disclose.
Activity of fenretinide/Lym-X-Sorb oral powder combined with the oral microtubule inhibitor ABT-751 against multidrug-resistant neuroblastoma xenografts
Authors: C. P. Reynolds, N. Tran, V. Maldonado, V. Khankaldyyan, H. Shimada, B. J. Maurer
Journal: Journal of Clinical Oncology (2008)

10031 Background: ABT-751, a colchicine binding-site microtubule inhibitor, and fenretinide [N-(4 hydroxyphenyl) retinamide, 4-HPR] are orally bioavailable drugs that have shown some clinical activity in recurrent neuroblastoma. Methods: We determined activity of ABT-751 + 4-HPR/Lym-X-Sorb oral powder against progressing subcutaneous xenografts in nu/nu mice from four recurrent (post- chemotherapy) neuroblastoma cell lines (SMS-KCNR, CHLA-90, CHLA-136, and CHLA-140) using an oral 5 day/week-dosing schedule. Apoptosis in tumors was assayed by TUNEL. Cytotoxicity in vitro employed the fluorescence-based DIMSCAN assay while reactive oxygen species (ROS) were measured by flow cytometry. Results: Combined results (median survival in days) from the four subcutaneous xenograft models (n = 5 per line for each condition) were: control = 28, 4-HPR = 49, ABT-751 = 77, and 4-HPR + ABT-751 = 239. Combining 4-HPR + ABT-751 significantly (p < 0.01) enhanced mouse survival (relative to controls or single drugs) in the subcutaneous models (with 5 day/week × 60–90 days and 7-day/3 week dosing schedules) and also in a CHLA-136 disseminated disease model in SCID mice. Tumor cell apoptosis by TUNEL was greater in 4-HPR + ABT-751 treated tumors than with single drugs. When 4-HPR + ABT-751 was stopped at day 66 (all SMS-KCNR mice in response), re-treatment of tumors progressing at day 169 again achieved responses. 4-HPR + ABT-751 was active against xenografts that had progressed on either drug alone. Interestingly, synergy between 4-HPR and ABT-751 in vitro was observed only in 2 of 6 neuroblastoma cell lines. In the CHLA-119 cell line, antioxidants ascorbic acid and α-tocopherol (but not n-acetylcysteine or sodium thiosulfate) suppressed ROS generated by 4-HPR and diminished the synergistic cytotoxicity of 4-HPR + ABT-751 in vitro. Conclusions: 4-HPR + ABT-751 is a well-tolerated oral drug combination that is highly active in vivo against multiple recurrent neuroblastoma xenograft models and warrants clinical trials. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Childrens Hospital Los Angeles Childrens Hospital Los Angeles
Dose-response relationship in phase I clinical trials: A European Drug Development Network (EDDN) collaboration study.
Authors: P. A. Cassier, V. Moreno Garcia, C. Gomez-Roca, D. Olmos, R. Morales, G. Del Conte, E. Gallerani, A. Brunetto, P. Schoffski, S. Marsoni, J. H. M. Schellens, N. Penel, E. E. Voest, T. R. J. Evans, R. Plummer, R. H. Wilson, J. Soria, J. Tabernero, J. Verweij, S. B. Kaye
Journal: Journal of Clinical Oncology (2011)

3084 Background: Alkylating agents have a strong dose effect relationship and this concept is used for development of novel cytotoxic (CTX) drugs. However, the need to reach MTD to obtain optimal benefit with molecularly targeted agents (MTA) is controversial. In this study we aimed to evaluate the relationship between dose and efficacy in a large cohort of phase I patients (pts) with refractory solid tumors. Methods: We retrospectively collected data on 2232 consecutive pts treated in phase I trials in 14 European institutions in 2005 - 2007. Inclusion criteria for this analysis were: a) pts treated within single agent studies where MTD was defined; b) RECIST response available. We used logistic and Cox regression models to study the relationship of dose (as continuous variable of % of MTD) with objective response rate (ORR), disease control rate (DC) and overall survival (OS). The clinical tumor growth rate (CTGR) - a log ratio of time between advanced disease diagnosis and phase I entry to number of treatment lines- was used to identify the impact of slow growing tumors on DC. Results: 1,015 pts were eligible (MTA 72%; CTX 28%). The ORR was 3% and DC at 3 and 6 months was 25% and 11%. Median CTGR was 22 weeks. There was no difference between ORR in pts receiving MTA or CTX but the DC rate at 3 and 6 months was higher for MTA (28% and 12%) than CTX (17% and 6%; p<0.01). This difference was attributed to the higher number of pts with slow growing tumors (CTGR > 20 weeks) treated with MTA (59%) vs. CTX (48%; p=0.001). Higher doses were associated with ORR to CTX agents (median dose: responders 92% vs. non-responders 62%; OR=6.4, p=0.06) but not to MTA. There was a relationship between dose and OS for CTX agents (univariate Cox regression HR=0.63 [95%CI 0.43-0.93], p=0.02) but not for MTA (HR=1.06 [95%CI 0.87-1.27], p=0.55). However in the multivariate model adjusted for clinical and demographic variables no relationship was found between dose and OS for either MTA or CTX. Conclusions: These results support current development of novel CTX agents based on MTD. We found no direct relationship between higher doses and ORR or OS with MTA in unselected pts. There is an urgent need to identify better biomarkers to guide dose escalation trials of MTA.
Phase II study of weekly topotecan in recurrent ovarian cancer: duration of response based on a prolonged follow-up
Authors: M. Marinaccio, E. Mele, A. Lepera, E. De Marino, E. Cicinelli, R. Catacchio, S. Schonauer
Journal: Journal of Clinical Oncology (2008)

16549 Background: Up to date the concept of “Stable Disease” (SD) as a clinical outcome is still considered a problematic endpoint. In a previous study we demonstrated that Topotecan, administered at a low weekly dosage (2,0 mg/m2) is an active option in the subset of heavily pretreated patients with recurrent platinum-resistant epithelial ovarian cancer (RprEOC) (Proc.ASCO, 2007; Abs. N°16076). In this phase II single arm trial, we explored the safety of the weekly topotecan with a particular interest in the duration of response, both in partial response and in stable disease. Methods: Nineteen patients (median age 52 yrs, range 45-72) with RprEOC who progressed after 3 (11/19 = 57.9%), 4 (7/19= 36.8%) or 5 (1/19= 5.3%) previous lines of chemotherapy were treated with Topotecan at the dose of 2.0 mg/m2 via a 30-minute i.v. infusion once every week until disease progression, unacceptable toxicity or when a stability of disease was reached. Results: All patients were evaluable for toxicity and clinical response. 16/19 pts enrolled (84.2%) had stage III-IV disease. Median number of chemotherapy cycles was 7 (range 3 - 12). A total of 107 cycles were administered. Dose reduction was necessary for 13% of the cycles. Main toxicities included anemia (grade I-II=57.9%), leucopenia (grade I-II=15.8%), thrombocytopenia (grade I-II=10.5%) and asthenia (20%). No one showed complete response, while 5/19 partial response (26.4%) and 6/19 stable disease (31.5%) were observed. 8/19 pts (42.1%) progressed on therapy. The median progression-free interval was 12 weeks in patients with partial response; stable disease was maintained for a median time of 14 weeks. Conclusion: Topotecan administered at low weekly dosage (2.0mg/m2) is an active option in the subset of heavily RprEOC and it seems also to be a very tolerable regimen compared to the classical 5-day schedule, characterized by an easy administration and absence of cumulative toxicities or cross-resistance In our experience the response obtained with this chemotherapeutic agent is of a particular interest because based on a prolonged follow-up. The rate of patients with ongoing stable disease (31.5%) suggests that the clinical benefit of weekly topotecan may be expected also in patients with no other viable therapeutic options. No significant financial relationships to disclose.
A phase II study of erythropoietin (EPO) with low dose dexamethasone (Dexa) for cancer related (CR) fatigue (F)
Authors: S. S. Hwang, V. T. Chang, Q. Xia, H. Yan, P. Osenenko, S. Srinivas, E. Morales, L. Duque, J. Cogswell, B. Kasimis
Journal: Journal of Clinical Oncology (2005)

8046 Background: Fatigue remains the most difficult symptom to treat in pts with advanced cancer. EPO and Dexa are active agents in palliating F, and may have synergistic effects on erythropoesis in vitro. The purpose of this study was to assess the combined palliative effect of EPO+Dexa on F in pts with metastatic solid tumors. Methods: Thirty four (34) anemic pts (Hgb 8–12 gm/dL) with F (usual F ≥ 3/10) not receiving concurrent chemotherapy received EPO 40,000 units SQ weekly and Dexa for 12 weeks (wks); the Dexa dose was reduced from 4 mg to 2 mg po daily after the first 7 pts. The pts completed BFI, FACIT-F, FACT-G and MSAS-SF every 4 wks. Improvements (imp) in FACIT-F by 4 points and Hgb by 2.0 gm/dL at any time during study were defined as F and Hgb responses. The Wilcoxon matched-pairs signed-rank test was performed. Results: Among 34 pts, 9 were excluded from analysis (3 refused, 3 expired early due to disease progression; 3 were withdrawn for deterioration in 2 pts and infection in 1 pt). Results in 25 evaluable pts were: Median (M) maximum (max) FACIT-F imp was 8 points (0–31) and M max BFI usual F imp was 3 points (0–7); 18 pts (72%) achieved max F imp by wk4. M max imp Hgb was 2.8 gm/dL (0.5 - 5.1) and 16 pts (64%) had Hgb response. The BFI usual and worst F, FACIT-F, KPS and FACT-G functional wellbeing (FWB) improved significantly (all p<0.05) by wk4 and remained stable at wk8, but significantly worsened by week 12 (p<0.05) (See Table). FACT-G SUMQOL and MSAS-SF measures showed similar trends. M survival length was 4.1 months. Hyperglycemia was the most frequent side effect (8 pts with grade 1–2; 2 pts with grade 3). Of the 7 initial pts who received Dexa 4 mg po daily, there were 3 episodes of sepsis. Conclusions: Eighteen (72%) pts had F response and 16 (64%) had Hgb response. Dexa at 4 mg po daily was associated with serious toxicity. Dexa at 2 mg po daily was well tolerated without major toxicity. A confirmatory phase III trial (ECOG E1Z01) is ongoing. Supported by Ortho Biotech. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ortho-Biotech
Use of PSA percent tumor dimensional markers to predict biochemical recurrence after radical prostatectomy in clinically localized prostate cancer.
Authors: R. Mizuno, J. Nakashima, K. Shinoda, H. Kono, E. Kikuchi, H. Nagata, H. Asanuma, A. Miyajima, K. Nakagawa, M. Oya
Journal: Journal of Clinical Oncology (2011)

e15134 Background: In prostate cancer(PCa), tumor volume(TV) has been thought to be a good candidate for predicting biochemical recurrence(BCR) after radical prostatectomy(RP). However, accurate volume measurement of this multifocal cancer is often difficult and time-consuming, leading some investigators to doubt its utility. To overcome this inconvenience, an alternative method of estimating tumor size was warranted. In the present study, we estimated tumor size by utilizing percent tumor diameter(PTD), percent tumor area(PTA), and percent TV(PTV), which were defined as (tumor size x 100)/prostate volume. We also made three new parameters, PSAPTD, PSAPTA, and PSAPTV by multiplying PSA and three tumor size parameters, PTD, PTA, and PTV. The present study was undertaken to investigate the prognostic implication of those tumor size parameters after RP. Methods: Serial whole sections of the prostate from 204 patients who underwent RP were investigated. The correlation of tumor size parameters with extraprostatic disease(EP) was assessed using logistic regression and receiver operating characteristics(ROC) analyses. Cox’s proportional hazard regression model was used for univariate and multivariate analyses to test the relationships between BCR and those clinicopathologic factors, including tumor size markers. Results: Logistic regression analysis demonstrated that PTD, PTA, PTV, PSAPTD, PSAPTA, and PSAPTV were significant predictors of EP. The ROC analyses for predicting EP showed that the areas under ROC curves of those tumor size markers were nearly equal. In multivariate Cox’s proportional analysis, Gleason score(GS)(p=0.0001), surgical margin status(SMS)(p=0.0042) and PSAPTD(<0.0001) were found to be independent indices for predicting BCR after RP. Conclusions: These results imply that the ability of those tumor size markers to predict EP is nearly equal. These results also suggest that PSAPTD is a significant independent predictor of BCR after RP along with GS and SMS. Since calculating tumor diameter on the slide glass is a rapid, simple and objective method, tumor diameter-based markers can be utilized instead of tumor volume-based markers.
Current patterns and costs associated with oral and injectable therapy for metastatic breast cancer in U.S. women: A SEER-Medicare analysis.
Authors: Hope S. Rugo, Karen Clements, Lisa McGarry, Claudio Faria, April H. Teitelbaum
Journal: Journal of Clinical Oncology (2013)

156 Background: A prior SEER-Medicare analysis (2001-2008 data) of injectable treatment (tx) after MBC diagnosis (dx) found fulvestrant was the most common 1st-line received (15% of patients) and vinorelbine the most common 2nd- and 3rd-line tx (17% and 13%, respectively). Lifetime cost of treating MBC averaged $110,000. The current study updates this analysis and focuses on a subgroup with prescription drug (Part D) Medicare coverage to evaluate tx patterns and costs including oral agents. Methods: Sample included women with breast cancer dx 2001-2007 with concurrent or subsequent MBC dx, Medicare enrollment from 12 mo prior to dx through 2009 or death, and indication of pharmacologic MBC tx. Subgroup with part D coverage and MBC diagnosis in 2007 was identified. Lines of tx were designated as: 1st-line if 1st agent (or combination if on same day) after dx of MBC; new agents administered &gt; 42 days after the previous agent are a new line, as well as an agent administered &gt; 60 days after last dose of the same agent. Costs were adjusted for length of follow-up. Results: Tx patterns in the overall sample were similar to prior results. Fulvestrant remained the most common 1st-line tx (19% of patients), and vinorelbine the most common 2nd- (18%) and 3rd-line tx (16%). Total costs ($127,000) were higher than in prior study. In the subgroup with Part D coverage (Table) use of oral agents was common for all tx lines. Mean lifetime treatment costs were lower than in overall sample ($102,000) and varied by treatment received. Conclusions: In this population, oral agents are common MBC tx. Inclusion of Part D claims provides a more complete picture of tx patterns in MBC. [Table: see text]