tbuckley/cabot-search huggingface dataset:
Changing physician compensation and implementing new technology to enhance pathways compliance.
Authors: Lalan S. Wilfong, John Russell Hoverman, Nate Gosse, Marcus A. Neubauer, Vanessa Torres
Journal: Journal of Clinical Oncology (2016)

187 Background: Pathways have shown to decrease cost of care while maintaining efficacy of treatment. In 2005, The US Oncology Network, which includes Texas Oncology, P.A. (TOPA) developed physician-led clinical pathways based on national guidelines, cost and efficacy. This abstract reviews the impact of changes TOPA initiated to improve pathway compliance Methods: Since 2011, TOPA has assessed pathways compliance using the iKnowMed (iKM) electronic medical record. Individual compliance was reported to each physician, but no incentives were tied to this. In 2015, the TOPA annual productivity bonus structure (2% of compensation) was changed to introduce pathways compliance and exception documentation thresholds, with penalties for sub-threshold performance. Additionally, TOPA sought to improve on iKM-based data collection and assessment. Previously, there were data challenges with pathways assessed retrospectively, offering limited visibility at the time of decision-making. In September 2015, new technology (Clear Value Plus – CVP) was embedded within iKM, which allowed prospective pathways assessment and provided real-time compliance reporting. Results: Introduction of individual incentives and improved decision support increased pathways compliance. For the initial yearly bonus measurement period, TOPA pathways compliance was 78%. After implementation of the new bonus structure, compliance increased significantly to 83% (p&lt;0.0001). Implementation of CVP further improved pathway compliance for comparable reporting periods from 78% in September 2014 to 90% in September of 2015 (p&lt;0.0001) Conclusions: We have shown that even a small change in compensation significantly influences physician pathways compliance. Additionally, technology to assist physicians with documentation and real-time assessment also significantly improves pathway compliance. [Table: see text] [Table: see text]
Clinical outcome of cN0 non-small cell lung cancer patients staged by thin-slice CT, FDG-PET, and EBUS-TBNA.
Authors: Y. Sakairi, H. Hoshino, T. Nakajima, T. Fujiwara, F. Ishibashi, H. Tamura, H. Wada, T. Iwata, T. Okamoto, T. Mizobuchi, Y. Moriya, S. Yoshida, K. Yasufuku, I. Yoshino
Journal: Journal of Clinical Oncology (2011)

7052 Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a qualitative minimally invasive diagnostic procedure, and has dramatically changed the practice of mediastinal staging of non-small cell lung cancer (NSCLC) as. We clarify the outcome of cN0 patients with preoperative staging system integrating EBUS-TBNA. Methods: From 2004 to 2010, EBUS-TBNA was performed in patient with NSCLC when mediastinal lymph nodes were radiologically positive; short diameter 10mm or more on thin slice CT, or standardized uptake value was 2.5 or more on PET scan. Resected cN0 NSCLC patients were enrolled for this retrospective study. The prognosis and the incidence of pathologic nodal metastasis was investigated from the prospective registry. Results: Five-hundred seventy-two patients were eligible as cN0 disease. Of them, 380 patients were radiologically negative for lymph node metastasis, and 192 were radiologically positive, but negative by EBUS-TBNA. EBUS-TBNA accurately diagnosed 81% of cN0 as true pN0. The main reason for EBUS-negative pN1/2 was existence of metastatic nodes in stations not amendable to EBUS-TBNA. The negative predictive value of EBUS-TBNA procedure for metastatic nodes was 93%. Median follow-up was 34.7 months. Among the cN0 patients, 5-year survival rates were 85% for the pN0 (n=490), 60% for the pN1 (n=42) and 67% for pN2 (n=40) (p=0.0001). The proportions and 5-year survival rates of patients classified by pathologic nodal status (pN0/1/2) were 88/6/6%, 88/80/77% (p>0.05) in radiologically negative cases and 81/10/9%, 79/45/54% (p=0.003) in radiologically positive but EBUS-negative cases. Conclusions: EBUS-TBNA reveals a large number of pN0 cases out of radiologically positive cases. pN2 cases sneaked through the staging system show favorable prognosis. A combination of PET/CT and EBUS-TBNA may obviate surgical staging in cN0 NSCLC patients.
Phase I study of BMS-599626, an oral pan-HER tyrosine kinase inhibitor, in patients with advanced solid tumors
Authors: L. L. Garland, M. Pegram, S. Song, D. Mendelson, K. E. Parker, R. E. Martell, M. S. Gordon
Journal: Journal of Clinical Oncology (2005)

3152 Background: BMS-599626 is an orally bioavailable inhibitor of the HER1, HER2 and HER4 tyrosine kinases (IC50=22, 32 and 190 nM, respectively). Methods: Patients (pts) with advanced solid tumors were administered BMS-599626 orally once daily, 21-days on, 7-days off per cycle. Initial eligibility requirements included tumor expression of HER2 by immunohistochemistry; after 6 pts were enrolled, this criterion was modified to include all pts regardless of HER2 status. Seven pts have been treated on 3 dose levels of 100, 200 and 320 mg/day. Results: As of November 22, 2004, safety and PK data are available for pts treated in the 100 and 200mg cohorts (3 pts per dose level). No dose limiting toxicities have been observed during cycle 1. Grade 1 or 2 at least possibly drug-related adverse events have been reported and include: diarrhea (1), nausea (3), vomiting (1), rash (1), fatigue (3), musculoskeletal pain/cramp (3), cough (3). In cohort 1 (100 mg dose), BMS-599626 had Tmax ranging from 1 to 8h (median 2h). Following single dose, geomean Cmax =162 ng/ml, mean AUC0-∞=2920 ng/ml hr. A healthy volunteer study revealed similar results following a single 100 mg dose, with Tmax, Cmax and AUC of 2 h, 120 ng/ml and 2610 ng/ml hr respectively. Day 8 and day 21 PK revealed similar Cmax and AUC0-∞ with respective geomean values of Cmax =352, and 377 ng/ml, and AUC0-∞=9050 and 8300 ng/ml hr, suggesting no significant accumulation in exposure over time. Terminal half-life was about 20 hrs. Exposure increase was linear from 100 mg to 200 mg dose levels. Conclusion: To date, BMS-599626 has been well tolerated and has a favorable PK profile for daily dosing. Dose escalation is ongoing. HER2 positivity will be reinstated as an eligibility criterion once the MTD has been established for further study in a dose expansion cohort. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb
Lessons learned from a cancer center-specific federal quality reporting program.
Authors: Stephen Flaherty, Denise Morse, Tracy Spinks, Sara Berger, Lisa M. Kidin, Thomas W. Ross
Journal: Journal of Clinical Oncology (2014)

42 Background: As part of the Affordable Care Act (ACA) of 2010, the Prospective Payment System-Exempt Cancer Hospital Quality Reporting (PCHQR) Program was created for 11 cancer centers. PCHQR includes an initial set of 5 measures mandated for federal reporting and expanded to include 18 measures for subsequent program years. The Alliance of Dedicated Cancer Centers (ADCC) formed in 1983 to include and represent the interests of the same 11 centers. As a small and previously organized group, we have been able to collaborate closely throughout implementation of PCHQR to understand, evaluate, and offer feedback on the program. Methods: The ADCC began sharing and reviewing data on mandated measures upon the release of the ACA in 2010. Numerator and denominator data for measures are manually uploaded from each center to a common master file bi-annually. In December 2013, ADCC hospitals formally began sharing feedback on concordant and non-concordant cases through email, bi-annual in person meetings, and monthly teleconferences. Results: Through sharing feedback on data submission with each other, CMS, and CMS contractors the ADCC learned the following lessons: 1- Limitations exist in the submission of our current data sets, (e.g. inability to accurately capture all scenarios that lead to appropriate delays in treatment). 2- Process of care measures are topped out with aggregated values above 95% for multiple consecutive quarters. 3- 4 of the existing measures and multiple forthcoming measures have case selection criteria creating sample sizes of little comparative value or statistical significance. 4- Tertiary care centers share many unique treatment patterns affecting compliance (e.g. lag time from referral to diagnosis, high percentage of patients on clinical trials). 5- Subject matter experts embedded at the 11 centers are critical for measure development/ refinement (e.g. Tumor Registrars, ICP’s). 6- CMS, CMS contractors, and affected hospitals must establish effective communication channels. Conclusions: Our early experiences indicate it is challenging to apply broad national measures to the ADCC hospitals. The 11 centers seek to continually improve upon this mandate and advance clinical practices.
Identification of a high-response patient population to S-1 via predictive enrichment strategy analysis of the S-CUBE phase III trial.
Authors: Masatoshi Kudo, Takuji Okusaka, Shuichi Kaneko, Junji Furuse, Madoka Takeuchi, Xuemin Fang, Yoshito Date, Masahiro Takeuchi
Journal: Journal of Clinical Oncology (2016)

229 Background: S-CUBE was a randomized, double-blind, phase III trial evaluating the efficacy and safety of S-1 in patients with sorafenib-refractory advanced hepatocellular carcinoma (HCC). The study’s primary outcome was presented at the 2015 ASCO Annual Meeting. Although S-1 did not significantly improve overall survival (OS) in all cohort (hazard ratio [HR] = 0.86; confidence interval [CI] = 0.67–1.10; P = 0.2201), we conducted predictive enrichment strategy analysis (PESA) to identify a patient population with a better response to S-1. Methods: Predictive enrichment strategy is a newly introduced concept proposed by the United States Food and Drug Administration, “to select a study population in which detection of a drug effect (if one is in fact present) is more likely than it would be in an unselected population. (Temple R. [2012] )” Therefore, in our study, PESA provides robust results and identifies advanced HCC patients who are more likely to respond to S-1. Clinically meaningful baseline characteristics were selected to create a scoring system; patients were ranked based on their scores, and the population with a better response was identified. Patient mapping was used to further characterize the population. Results: The full S-CUBE analysis set consisted of 333 patients, including 222 in the S-1 arm and 111 in the placebo. PESA and patient mapping identified 219 patients (65.8% of the total population) as the high-response patient population. High-response patients are classified as those with the following criteria; 1) TNM stage III, IVa, or IVb, 2) Child-Pugh class A, and 3) Levels of both the tumor markers are not high (AFP ≥ 400 ng/mL and PIVKA-II ≥ 10000 mAU/mL). In this population, the median OS of S-1 group was significantly longer than that of placebo group (426.0 days vs. 375.5 days; HR, 0.69; 95% CI, 0.51 to 0.93; P = 0.0156). Conclusions: PESA and patient mapping identified a high-response patient population to S-1. This statistically robust analysis demonstrated S-1 showed survival benefit for identified clinically-important population of sorafenib-refractory advanced HCC patients. Clinical trial information: JapicCTI-090920.
Hypofractionated radiotherapy for oligometastatic non-small cell lung carcinoma.
Authors: M. D. Hasselle, K. E. Rusthoven, B. D. Macrie, N. Shah, D. W. Golden, R. R. Weichselbaum, J. K. Salama
Journal: Journal of Clinical Oncology (2010)

e18049 Background: Outcomes data on treatment of oligometastatic (OM) non-small cell lung carcinoma (NSCLC) with hypofractionated image guided radiotherapy (HIGRT) are limited. Methods: Consecutive OM NSCLC patients were reviewed. Treatment of all active disease was required. Lesions receiving prior radiation or with radiographic/metabolic resolution after chemotherapy were inactive, and did not receive HIGRT. Time to progression (TTP) was defined as time from the start of HIGRT to any failure. Local failure was defined as ≥20% increase in size on single dimensional axial measurement. Lesion control (LC), TTP, progression-free survival (PFS), and overall survival (OS) were estimated using the Kaplan-Meier method. Multivariate analysis (MVA) was performed using Cox proportional hazards regression. Results: Of 26 patients screened, 24 met the inclusion criteria. Median follow-up was 12.4 months. Median age was 66 yrs. Ten patients had adenocarcinoma, 14 had newly diagnosed stage IV disease, and 11 received HIGRT for progressive disease (PD) after chemo. Eighteen patients received systemic therapy prior to HIGRT, having received an average of 1.3 regimens. Seventeen patients received HIGRT to all disease and 7 received treatment to active disease only. A median of 2 (range 1-5) OM lesions were treated per patient. Median OS and TTP were 16.7, and 8.1 months, respectively. The 1 yr OS and PFS were 76.7% and 48.1%, respectively. On MVA, newly diagnosed stage IV disease independently predicted TTP (HR 0.22, p = 0.04). Fifty-eight individual lesions were treated, with a median size of 2.65cm (range 0.6 to 9.6 cm). Median total and fraction dose were 42 (range 18-70) and 8 Gy (range 3.5-18), respectively. The 1 yr LC was 84%. The calculated median standard equivalent dose (SED) in 2 Gy fractions was 64.6 Gy for extracranial lesions. SED ≥ 64.6 Gy was associated with a trend towards increased control (18 mo LC 89 vs 52%, p = 0.06). Two patients experienced grade 3 toxicity. Conclusions: Treatment of OM NSCLC with HIGRT is safe and provides durable LC when sufficient doses are used. Future studies should be aimed at optimizing patient selection for HIGRT and integration with systemic therapy. No significant financial relationships to disclose.
Integrated genomic correlates of response to PD-1 inhibitor nivolumab in metastatic renal cell carcinoma (mRCC).
Authors: Guillermo de Velasco, Diana Miao, Sachet Shukla, Martin Henner Voss, Catherine Wu, Bradley Murray, Matthew Meyerson, Sabina Signoretti, Robert J. Motzer, Eliezer Mendel Van Allen, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2016)

545 Background: Nivolumab (nivo) is a programmed death-1 (PD-1) inhibitor that has recently been shown to increase overall survival in patients with mRCC. The association between benefit from nivo with neoantigen load, mutation load and signatures of immune infiltration has yet to be explored in mRCC. Methods: Publicly available whole exomes (WES) and whole transcriptomes (RNA-seq) from over 300 clear-cell RCC patients in the Cancer Genome Atlas (TCGA) were analyzed for mutational load, neoantigen load and expression of immune-related genes. HLA types were inferred from WES with Polysolver and neoantigens were predicted from somatic nonsynonymous mutations with NetMHCpan3.2. The same analysis pipeline was applied to paired pre-treatment germline and metastatic tumor specimens from 9 patients who received nivo for mRCC: 3 responders (CR or PR by RECIST; R) and 6 non-responders (SD or PD by RECIST; NR), all with available pre-nivo fresh biopsies of metastatic lesions. Matched RNA-seq was available on a subset of these patient samples (3 R, 3 NR). Results: Across the TCGA and nivo-treated patients cohorts, RCC had relatively few nonsynonymous mutations and neoantigens. Among the nivo-treated patients, neoantigen load was significantly higher in NR compared to R (p = 0.048), but nonsynonymous mutation load was not. An exceptional R who experienced CR (PFS &gt; 30 months) had outlying higher expression of selected immune-related genes compared to the 8 other patient samples (p &lt; 0.05 for PD-L1, PD-L2; p &lt; 0.01 for CTLA4, PD-1, PRF1; p &lt; 0.001 for GZMA, BTLA, CD8A), and was in the top 1-5% of expression of these genes among all TCGA data. Bootstrapping analysis comparing mean expression in R vs NR compared to an empirical distribution of TCGA RNA-seq data showed significantly higher expression of PD-1, PD-L1, GZMA, LAG3, IDO1, ICOS, and BTLA in R vs. NR (p &lt; 0.05). No genes were enriched for nonsynonymous mutations in R or NR. Conclusions: This analysis suggests that both DNA- and RNA-level data may be relevant for explaining clinical benefit from nivo in mRCC. In contrast with results from other tumor types, responders to nivo did not have more mutated tumors, though immune-related gene expression may be related to response.
p53 as an additional marker to the intrinsic subtype classification as a method to further stratify breast cancer survival in African American (AA) women
Authors: K. A. Dookeran, Y. Wang, X. Gao, K. Ferrer, M. Sekosan, B. Lukaszczyk, E. K. Radeke, W. McCaskill-Stevens, H. A. Zaren, S. Gehlert
Journal: Journal of Clinical Oncology (2008)

22007 Background: We hypothesized that breast cancer survival using the intrinsic subtype classification (i.e. luminal A/B type [A=ER+, &/or PR+, & HER2−; B=ER+, &/or PR+, & HER2+], HER2+ type [ER−, PR−, & HER2+], & basal type [ER−, PR−, HER2−, cytokeratin 5/6+ &/or HER1+]) in AA women, could be further stratified using p53 status. This potentially would allow identification of women with poorer prognosis. Methods: Tumors from 331 consecutive low socioeconomic status AA women treated between 1/00–12/05 were evaluated for subtype and p53 (Pab1801 antibody) status with IHC on paraffin embedded tissue. Survival comparison was computed using Log-rank test and Cox proportional-hazards model (hazard ratios [HR] & 95% confidence intervals [CI]). Results: Overall 31% (101) women were age <50 yrs, 69% (230) were ≥50 yrs, and 29% had p53+ status. At median follow-up of 37 months, women with p53+ tumors had significantly worse survival (HR=1.813; 95% CI=1.148–2.864; p=0.011). This adverse p53 survival effect however was confined to women aged <50 yrs (HR=4.374; 95% CI=2.036–9.396; p<0.001). Compared to luminal A/B type, women with basal type had the poorest survival (HR=2.363; 95% CI=1.478–3.779; p<0.001). For women age <50 yrs and compared to a reference group with luminal A/B & p53- type tumors, HRs were highest and survival was significantly worse for all subtypes with p53+ status (see table). Conclusions: p53 status appeared to enable further stratification of breast cancer survival for intrinsic subtypes in AA women age <50 yrs. These findings may allow identification of women with poorer prognosis within each major subtype category, although results are limited by small sample size. Further validation in a larger study population is suggested. HRs for Subtypes ± p53 Status in AA Women < 50 yrs Subtype HR 95% CI P Value LUMINAL A/B P53+ 7.947 1.945-32.464 0.004 HER2+ P53− 1.668 0.186-14.974 0.648 HER2+ P53+ 9.459 1.689-52.971 0.011 BASAL P53− 4.854 1.360-17.323 0.015 BASAL P53+ 14.991 3.820-58.830 < 0.001 No significant financial relationships to disclose.
Antitumor activities of bevacizumab for <i>KRAS</i>, <i>BRAF</i>, and <i>PIK3CA </i>mutated human colorectal cancer xenograft models.
Authors: Suguru Harada, Mieko Yanagisawa, Toshiki Iwai, Satoshi Aida, Mitsue Kurasawa, Keigo Yorozu, Kaname Yamamoto, Naoki Harada
Journal: Journal of Clinical Oncology (2013)

362 Background: In colorectal cancer, it has been reported that mutations (mts) in KRAS, BRAF, or PIK3CA can have a negative impact on molecular target therapies. Especially, a KRAS mt represents a predictive biomarker for resistance to anti-EGFR antibodies. Bevacizumab (BV), an anti-VEGF-A antibody, has been demonstrated to have clinical benefits in colorectal cancers; however, the impact of mts in especially BRAF or PIK3CA on the efficacy of BV remains unknown. In this study, we examined the antitumor activity of BV in human colorectal cancer xenograft models harboring these mts. Methods: BALB-nu/nu mice were subcutaneously inoculated with 15 colorectal cancer cell lines. BV was intraperitoneally administered every week for 3 weeks at a dose of 5 mg/kg. Antitumor activity was evaluated by determining tumor volume and tumor growth inhibition (TGI) on day 22. The colorectal cancer cell lines used were screened for KRAS, BRAF, and PIK3CA mts by direct sequencing of hot spots. Statistical analysis was performed using Wilcoxon test for tumor volume and TGI and Fisher's exact test for the correlation of genotype and antitumor effect. Results: Genotypes of KRAS, BRAF, and PIK3CA were all wild-type (wt) in COLO320DM, KM-12 and SW48 and in other cell lines were, respectively, as follows: COLO205, HT-29, WiDr and LS411N: wt, mt, and wt; SW620 and LoVo: mt, wt, and wt; HCT-8, HCT116, DLD-1, T84 and LS174T: mt, wt, and mt; RKO: wt, mt and mt. BV as a non-responder (NR) showed no significant antitumor activity in 3 cell lines (WiDr, LoVo and DLD-1), whereas as a responder (R) significant activity was observed in the other 12 cell lines. There was no significant difference in the antitumor effect of BV between cell lines depending on KRAS, BRAF or PIK3CAmutational status in terms of TGI and R/NR ratio (Table). Conclusions: BV shows antitumor effect regardless of mutational status of KRAS, BRAF, or PIK3CA in colorectal cancers. [Table: see text]
Impact of number of lines of prior chemotherapy in patients (pts) with advanced urothelial carcinoma (UC) receiving salvage therapy.
Authors: Guru Sonpavde, Joaquim Bellmunt, Jonathan E. Rosenberg, Dean F. Bajorin, Ashley Marie Regazzi, Toni K. Choueiri, Angela Q. Qu, Guenter Niegisch, Peter Albers, Andrea Necchi, Giuseppe di Lorenzo, Ronan Fougeray, Yu-Ning Wong, Srikala S. Sridhar, Yoo-Joung Ko, Matthew I. Milowsky, Matt D. Galsky, Gregory Russell Pond
Journal: Journal of Clinical Oncology (2014)

353 Background: The prognostic impact of number of lines of prior chemotherapy and prior perioperative chemotherapy on survival results in salvage trials for advanced UC is unknown. Methods: We pooled 10 prospective phase II trials of salvage therapy for advanced UC with data on the number of prior lines of therapy in addition to known prognostic factors: TFPC (time from prior chemotherapy), Hb (hemoglobin), PS (performance status), and LM (liver metastasis) status. Cox proportional hazards regression was used to evaluate the association of number of prior lines with overall survival (OS) and progression-free survival (PFS). Trial was included as a stratification factor. Sub-analysis examined the impact of prior perioperative chemotherapy. Results: Of 731 pts, data for all factors was available for 711. The overall median PFS and OS were 2.7 and 6.8 months, respectively. Trials evaluated vinflunine (N=151), docetaxel +/- vandetanib (N=147), paclitaxel-gemcitabine (N=83), sunitinib (N=77), nab-paclitaxel (N=48), volasertib (N=46), everolimus (N=45), pazopanib (N=43), cetuximab +/-paclitaxel (N=39) and paclitaxel-cyclophosphamide (N=32). The number of prior lines of therapy were 1 in 559 (78.6%), 2 in 111 (15.6%), 3 in 29 (4.1%), 4 in 10 (1.4%) and 5 in 2 (0.3%) pts. Prior perioperative chemotherapy was given to 277 (39.1%) and chemotherapy for metastatic disease to 454 (64.1%) pts. While TFPC, Hb, PS and LM were significantly associated with OS and PFS on multivariate analyses, the number of prior lines was not associated with OS (HR 0.99 [95% CI: 0.86-1.14]) or PFS (0.92 [0.80-1.05]). Prior peri-operative chemotherapy was a favorable factor for both OS and PFS on univariable but not multivariable analysis. Conclusions: The number of prior lines of therapy and prior perioperative chemotherapy were not independently prognostic for OS or PFS in UC pts receiving salvage therapy, although the data are limited by few pts with &gt;2 prior regimens. We infer that interpretation of OS and PFS results in salvage therapy trials will not be affected by inclusion of pts with ≥ 2 prior regimens including perioperative and/or metastatic disease treatment. These data need external validation.