tbuckley/cabot-search huggingface dataset:
Correlation of the prognostic impact of Ki67/BCL2 index based on immunohistochemistry with poor clinical outcome in gastric cancer.
Authors: Byoung Kwan Son, Kyueng Whan Min, Dong-Hoon Kim, Eun-Kyung Kim, Junghoon Ha
Journal: Journal of Clinical Oncology (2016)

61 Background: Considering the heterogeneity of gastric cancer, it is particularly important to identify potential prognostic indicators. Ki67 and B-cell lymphoma 2 (BCL2) proteins are known prognostic markers in different types of cancer. Ki67 is associated with cell proliferation, whereas BCL2 has anti-proliferative roles. A combined marker based on these opposite functions might provide improved prognostic information in gastric cancer. The aim of this study is to investigate correlations between a combined marker using Ki67 and BCL2 and clinicopathologic parameters, and to evaluate the prognostic value of the combinatorial marker in patients with different types of gastric cancer. Methods: This study assessed Ki67 and BCL2 expression using tissue microarray obtained from 276 patients with adenocarcinoma of the stomach. A Ki67/BCL2 index based on the relative expression of each protein was divided into low- and high-risk groups using receiver operating characteristic (ROC) curves. Results: High Ki67/BCL2 index was significantly associated with advanced AJCC stage, high recurrence, diffuse or mixed type, high histological grade, and the presence of lymphatic and perineural invasion (all p &lt; 0.05). Univariate and multivariate analyses revealed a significant relationship between disease-free or overall survival and Ki67/BCL2 index in intestinal-type gastric cancer(all p &lt; 0.05). Conclusions: A combined marker using Ki67 and BCL2 could be a useful indicator for predicting survival in patients with intestinal-type gastric cancer.
Can the combination of temsirolimus and bevacizumab improve the treatment of metastatic renal cell carcinoma (mRCC)? Results of the randomized TORAVA phase II trial.
Authors: B. J. Escudier, S. Negrier, G. Gravis, C. Chevreau, R. Delva, J. Bay, L. Geoffrois, E. Legouffe, E. Blanc, C. Ferlay
Journal: Journal of Clinical Oncology (2010)

4516 Background: Temsirolimus (T) and bevacizumab (B) have been approved for the treatment of mRCC. The T-B combination has proven feasible at full doses of each agent with promising activity in phase I. This study was aimed to promptly determine whether this combination could improve the results of available treatments. Methods: Untreated mRCC patients (pts) with ECOG PS £ 2 and measurable disease were randomized using a 2:1:1 ratio to T-B combination (arm A), sunitinib (arm B) or bevacizumab and a-interferon (arm C) in an open label, multicenter, non comparative phase II trial. Pts were treated until disease progression or unacceptable toxicity. The primary objective was to estimate the non-progression rate at 48 weeks (NPR-48) for arm A. Using Fleming's single-stage procedure and a NPR- 48 of 50% as the minimum needed for the combination to warrant further study, the planned sample size for arm A was 80 pts (assuming NPRs-48 of 35% in the pivotal trials [Motzer et al 2007, Escudier et al 2007]). Major secondary endpoints were toxicity, response rate (RR) and survival. Results: From 03/2008 to 05/2009, 171 pts were randomized: 88 (51%), 42 (25%) and 41 (24%) to arms A, B and C, respectively. Treatments were prematurely stopped for other reasons than progression in 43% (A), 12% (B) and 23% (C). Grade 3/4 events were observed in 36%, 14% and 27% pts in arms A, B, C respectively; two toxic deaths occurred in arm A. In an intent-to-treat analysis with a median follow-up of 43 weeks, NPRs-48 were 43.2% (95% CI, 32.7-54.2), 47.6% (95% CI, 32.0-63.6) and 65.9% (95% CI, 49.4-79.9) in arms A, B and C respectively. Best RRs (RECIST) were 25%, 24% and 34% respectively. Conclusions: The toxicity profile of the T-B combination was higher than expected, leading to a high drop-out rate. The results do not suggest any evidence of a synergistic/additive efficacy of this combination. Patients continue to be followed and updated data will be reported. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AVEO, Bayer, GlaxoSmithKline, Novartis, Pfizer, Roche, Wyeth Bayer, GlaxoSmithKline, Novartis, Pfizer, Wyeth GlaxoSmithKline, Roche, Wyeth
Role of adjuvant radiation therapy in ampullary carcinoma: Propensity-score matched SEER analysis.
Authors: John Byun, Surbhi Grover, Lauren Michelle Hertan, Smith Apisarnthanarax
Journal: Journal of Clinical Oncology (2014)

282 Background: Ampullary cancer outcomes have been reported to compare favorably with pancreatic and biliary malignancies. Consensus guidelines on the optimal adjuvant management after resection in these patients remain unclear. Propensity score matching was used to compare the outcomes of patients with ampullary cancer receiving or not receiving radiation therapy (RT) from the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Patients with a diagnosis of ampulla of vater carcinoma who underwent curative intent surgery were identified within 17 SEER registries from 1998-2008. Patients with M1 disease or follow up less than 5 months were excluded. Data on patient characteristics such as age at diagnosis, race, tumor characteristics including TNM staging and histologic subtype, and survival outcomes were extracted and compared between patients who received adjuvant RT and those who did not. Propensity score matching was used to minimize treatment selection bias within the specified characteristics and estimate the impact of RT on median survival times (MST). Matching algorithms used validated Mahalanobis nearest neighbor methods based on conditional probabilities of receiving RT. Results: Of the 1782 patients identified, 490 (25%) were treated with adjuvant RT: 318 (65%) T3/4 and 333 (68%) N1. Cox regression with propensity score analysis for patients with RT showed an overall decrease in survival time by 3.67 months (p&lt;0.05). Propensity score analysis showed slightly worse survival in patients who received RT compared to those who did not (MST 2.7 vs. 3.0 years, respectively, p=0.04). There was a trend towards a survival benefit with RT in a subgroup of patients over the age of 66 years with T2N0 tumors (MST 4.7 vs. 2.7 years, respectively, p=0.14). Survival outcomes analyzed by other T and N stages were not statistically significant. Conclusions: Adjuvant RT does not confer a survival benefit in resected ampullary cancers as studied in the propensity-score adjusted SEER patient population. Further studies should be conducted in order to elucidate the role of adjuvant RT for ampullary cancers.
The impact of subsequent metastasis on survival in Medicare patients with prostate cancer.
Authors: Tracy Li, Neal D. Shore, Maneesha Mehra, Mary Beth Todd, Ryan Saadi, Gaetan Leblay, Robert Griffiths
Journal: Journal of Clinical Oncology (2016)

94 Background: This study assessed the impact of subsequent metastasis on survival in Medicare prostate cancer (PC) patients initially diagnosed with locoregional disease. Methods: Using data from the United States Surveillance, Epidemiology, and End Results (SEER) cancer registry linked to Medicare claims, we identified patients diagnosed with locoregional PC between 2000 and 2011, age ≥ 66 at diagnosis, and who first had a diagnosis of metastasis ≥ 4 months after PC diagnosis (cases). Cases were matched to controls (patients without metastasis) in a 1:4 ratio to assess the incremental impact of developing metastasis. For each control, the timeline to develop metastasis was matched to the cases. Kaplan-Meier (K-M) analysis was used to compare all-cause, cancer-specific, and other-cause mortality between cases and controls. Cox proportional hazards regression was used to adjust for other factors associated with all-cause mortality. Results: There were 10,370 cases and 39,200 controls. Mean age at baseline was 79 years in each group. Among the cases, the median time to first metastasis was 37 months, 85% had bone metastasis, and the median survival time (months) after metastasis was 18 months compared to 118 months for controls (P &lt; 0.0001: Log-Rank). In K-M analysis, metastasis was associated with significantly (P &lt; 0.0001: Log-Rank) higher all-cause, cancer-related, and other-cause mortality. In multivariable survival analysis, metastasis was associated with increased all-cause mortality (HR = 4.6, 95% CI = 4.4-4.7, P &lt; 0.0001). High risk disease (based on Gleason score, comorbidity Index, and performance status) and delayed diagnosis of metastases were associated with worse survival. Conclusions: Development of metastasis in elderly PC patients diagnosed with locoregional disease significantly increases mortality.
Cost-effectiveness of routine laparoscopic ultrasound for the assessment of resectability of gallbladder cancer.
Authors: Thejus T. Jayakrishnan, Hasan Nadeem, Ryan Thomas Groeschl, Anthony J Zacharias, T. Clark Gamblin, Kiran Turaga
Journal: Journal of Clinical Oncology (2014)

272 Background: In addition to a diagnostic laparoscopy (DL), aroutine laparoscopic ultrasound (LUS) has been proposed to identify undetected hepatic metastases and/or anatomically advanced disease in patients with T2 or higher gall bladder cancer (GBC) planned for surgical resection. It was hypothesized that a routine LUS is not a cost-effective strategy for these patients. Methods: Decision tree modeling was undertaken to compare DL-LUS vs. DL at the time of definitive resection of GBC (with no prior cholecystectomy). Costs in US dollars (payers’ perspective), quality-adjusted-life-weeks (QALWs) and incremental-cost-effectiveness-ratios (ICER) were calculated (horizon: 6 weeks, willingness-to-pay: $1,000/QALW or $50,000/ QALY). Results: DL-LUS was cost effective at the base case scenario (costs: $30,838 for DL vs. $30,791 for DL-LUS and effectiveness 3.81 QALWs DL vs. 3.82 QALW DL-LUS, resulting in a cost reduction of $9,220 per quality adjusted life week gained (or $479,469 per QALY). DL-LUS became less cost effective as the cost of ultrasound increased (threshold: $163.18) or the probability of exclusion from resection decreased (threshold 0.29) (Table represents the results of univariate analyses). Conclusions: Routine LUS with diagnostic laparoscopy for the assessment of resectability and exclusion of metastases is cost effective for patients with GBC. Until improvements in pre-operative imaging occur to decrease the probability of exclusion, this appears to be a feasible strategy. [Table: see text]
Prescribing preferences (PPrefs) of U.S.-based medical oncologists (MOs) for choice of therapy after failure of first-line FOLFOX plus bevacizumab (FFB) in patients with metastatic colorectal cancer (MCC).
Authors: Johanna C. Bendell, Susan L. Britton, Maria Lankford, Arden Buettner, Mark R. Green, Douglas Neely, Mitchell Scharf
Journal: Journal of Clinical Oncology (2014)

533 Background: Phase III trials have tested biologic (bio) agents (bevacizumab [bev], anti-EGFR antibodies, ziv aflibercept [ziv]) plus chemotherapy (CT) vs. CT alone after failure of first-line therapy in patients given CT + bev first line. Several have shown improvements in progression-free and overall survival (OS) with the CT + bio approach, but it is not clear how these therapies are being used in the “real life” setting. Methods: Since 3/2013 PPrefs for this setting among 276 MOs were studied using a validated, proprietary, live, case-based market research tool. A core scenario and variations based on KRAS status and first-line therapy outcome were tested (S1, S2, S3, S4). PPref data acquired using blinded audience response technology. All sources of research support were blinded. Core scenario: 49 yr old female with cecal mass, liver/lung metastases, confirmed wt KRAS for S1-3, given FFB first line. S1: FFB x 16 wks → excellent PR → 5FU bev X 16 wks → progressive disease [PD]; S2: FFB x 16 wks → excellent PR → bev alone x 16 wks → PD; S3: FFB → stable disease [SD] x 5 months as best response [BR] → PD; 4) Here changed to mutKRAS; FFB x 8 wks → PD as BR. Results: Findings shown below (Table). Conclusions: In scenarios with wt KRAS, first-line response to FFB, a majority plan bev again second line. If BR to FFB is SD in WT KRAS, anti-EGFR antibody-based therapy is used more often. In S 1-3, ziv is the PPref of 7 - 14% of MOs studied. With mutKRAS and PD as BR to FFB, use of an antiangiogenic + second-line CT is preferred by &gt; 80%, nearly equally split between bev and ziv. Recent phase III trial data showing OS benefits are reflected in current MOs first failure PPrefs. [Table: see text]
Specialized outpatient palliative care: Results from a representative survey among physicians in Germany.
Authors: Jens Hermann Papke, Eberhard A Lux, Kerstin Marggraf, Ruth Fricker
Journal: Journal of Clinical Oncology (2014)

143 Background: Specialized ambulatory palliative care (SAPV) allows patients with incurable diseases and limited life expectancy to be cared for until death in their familiar surroundings. In Germany, these services must be prescribed by a physician. Little is known about structure, organization and work pattern within the SAPV teams. Methods: An online survey was carried out between Sept. 2013 and March 2014 with 124 physicians in Germany with regard to aspects related to physicians’ qualification, networks and palliative care teams. Aim of this survey was to evaluate status quo of SAPV from physicians´ viewpoint. Results: All 124 respondents were enrolled in SAPV; 18.3% of them (n=22) were on a direct contract with a health insurance provider. An additional qualification for palliative medicine and for pain therapy was reported by 96.7% and 21.5% of the physicians, respectively. In average, 11.6 physicians are organized in a SAPV-network. The networks comprise general practitioners (in 88.6% of the networks) anesthesiologists (in 62.3%), hematologists/oncologists (in 57.9%) and internists (in 43.9% of the networks) as well as a large proportion of non-medical professions such as pastors, pharmacists, social workers, psychologists and nurses. In most cases, SAPV networks are linked to one or more medical practices, hospitals or welfare institutions. 96% of the respondents assessed the cooperation within the network as “very good”/“good”. Patients admitted to SAPV were mostly suffering from cancer, but also from cardiovascular, neurological and respiratory diseases. The mean duration of care was 26.6 days; 81.4% of them could die in familiar domestic surroundings. On average, one physician is treating 9.7 SAPV-patients at the same time. Documentation requires 25.9% of time spent for medical care. Problems concerning reimbursement were reported by 75.8% of respondents. Conclusions: This survey provides the status quo of the German SAPV concept. Physicians enrolled in SAPV are highly qualified for palliative care and pain therapy. SAPV is a domain of outpatient care sector. While interdisciplinary cooperation within the SAPV networks is good, documentation and reimbursement remains a problem.
Subcapsular prostate cancer: Identification with mpMRI and MRI/TRUS fusion-guided biopsy.
Authors: Anna Mary Brown, Sandeep Sankineni, Arvin Koruthu George, Soroush Rais-Bahrami, Bradford J. Wood, Maria J Merino, Peter A. Pinto, Peter L. Choyke, Baris Turkbey
Journal: Journal of Clinical Oncology (2015)

52 Background: The subcapsular region is often under-sampled by standard 12-core transrectal ultrasound (TRUS) prostate biopsy. We retrospectively evaluated multi-parametric MRI (mpMRI) features of subcapsular prostate cancers (PCa) and their detection on MRI/TRUS fusion-guided biopsy (FgBx). Methods: All patients referred for 3T mpMRI and subsequent FgBx under an IRB-approved protocol from Jan 2010 to July 2014 were reviewed. Histologically confirmed subcapsular lesions (just inside the prostate capsule with capsular border length &gt;&gt; width) were identified. Impact of the FgBx on clinical management according to current National Comprehensive Cancer Network (NCCN) guidelines was evaluated, with prior status based on outside TRUS biopsy results. Results: Of 992 eligible patients, 33 had subcapsular prostate lesions on mpMRI. In this subpopulation, mean age, PSA, and prostate volume were 63 years (range 52-76), 8.4ng/mL (1.2-63), and 53 mL (12-125). The FgBx, consisting of targeted (TBx) and systematic (SBx) portions, confirmed PCa in 24 of 33 patients. Five cancers (21%) were only detected by TBx. The remaining 19 were diagnosed on both TBx and SBx, but in 5 of these 19 (26%), higher Gleason scores were found on TBx cores. The FgBx results more accurately classified patients’ NCCN risk scores, with 17 prior unknown or low risk PCa upgraded to higher risk scores (Table). Conclusions: Subcapsular lesions on mpMRI are rare but largely malignant. Most are found on 12-core SBx, but ~20% require TBx for diagnosis, and TBx more accurately grades &gt;25% of the lesions. The FgBx may improve clinical management of patients with subcapsular PCa, since more aggressive cancer was found in 17 of 24 patients. [Table: see text] [Table: see text] [Table: see text]
The standardization of skin cancer treatment recommendations through the analysis of clinical pathways data and an evidence-based, physician-driven committee process.
Authors: Dwight Earl Heron, Amanda Barry, Hans Benson, Zach Lorinc, Kathleen Lokay
Journal: Journal of Clinical Oncology (2016)

147 Background: Clinical pathways (CP) have the potential to improve the quality and safety of care and lead to more predictable outcomes and costs through standardization. Via Oncology’s CP program aims to standardize care at radiation centers across its nationwide network. Created through an evidence-based, physician-driven committee process, CP recommend the best treatment plan for specific patient populations based on a hierarchy of efficacy, toxicity, and cost. In the absence of definitive data, reaching a consensus on the best treatment recommendation is difficult, particularly for disease states such as melanoma, squamous cell carcinoma, and basal cell carcinoma for which a wide range of radiation doses and schedules are considered effective and regional and institutional preferences may vary. Methods: After initial implementation of CP, radiation disease committees meet semiannually to review treatment recommendations and utilization data collected for the prior six months. Data reflect treatment plans selected by physicians for individual patients. At the January 2015 skin pathway committee meeting, committee members reviewed data for each patient presentation to determine which doses and schedules were used most frequently. Results: After reviewing the utilization data, the committee narrowed the recommendations to one or two treatment plans per presentation, typically including standard and hypofractionated schedules. In scenarios where multiple treatment plans were selected at a similar frequency, the committee standardized to the lower dose and fewer fractionation plan. This reduced the number of treatment plans on the pathway from 34 to 15. A decrease in pathway adherence rates was not observed following this change. Conclusions: Data gathered from CP can be used to further standardize clinical care when there are several effective and accepted treatment regimens but a lack of published data. Through a dynamic process of assessing and modifying physician practice and patterns of care, CP provide cancer centers with a platform to ensure delivery of consistent, high-quality care to patients throughout their network.
High-dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation (HSCT) for patients with rhabdomyosarcomas (RMS).
Authors: F. Peinemann, M. Hildebrandt, M. Kulig, A. Herrmann-Frank
Journal: Journal of Clinical Oncology (2010)

e20527 Background: Patients with advanced RMS have a poor outcome. Treating these patients with HDCT followed by autologous HSCT is regarded experimental. The aim of this study was to evaluate the results from controlled trials. Methods: We systematically searched MEDLINE, EMBASE, and CENTRAL from inception to May 2009 without limits on study type and language. The primary outcome was overall survival (OS). Test intervention was defined as HDCT followed by autologous HSCT and control intervention was defined as chemotherapy without HSCT. Results: We identified 4 controlled trials on RMS with autologous HSCT. OS at 5 years ranged from 22% to 73% in the transplantation groups vs. 18% to 67% in the control groups. Two studies reported a statistically significant difference between both treatment groups. However, the results were contradictory. In one trial, OS in test vs. control group was estimated 53% vs. 18% and in the other trial 22% vs. 55% at 3 years. Age and disease stage were comparable and evaluation of more characteristics did not explain the conflicting results. Two more trials did not report a statistically significant difference between the treatment groups. The risk of bias was high in all 4 studies due to methodological flaws. Conclusions: The evidence base is not sufficient to support the use of HDCT followed by autologous HSCT for treatment of patients with RMS. Controlled trials had a high risk of bias and showed conflicting results. No significant financial relationships to disclose.
A phase I trial of the combination of erlotinib and tipifarnib in patients with advanced solid tumors
Authors: C. X. Ma, G. Croghan, J. Reid, L. Hanson, S. Mandrekar, R. Marks, A. Adjei, A. Furth
Journal: Journal of Clinical Oncology (2005)

3000 Background: Preclinical data indicates that the EGFR tyrosine kinase inhibitor erlotinib demonstrates greater than additive cytotoxic effects in combination with the farnesyl transferase inhibitor (FTI), tipifarnib (R115777, Zarnestra), and blocks the PI3-K/Akt pathway which has been implicated in tumor resistance to tipifarnib. The goal of this phase I study was to determine the maximum tolerated dose (MTD), pharmacokinetics (PK), and pharmacodynamics of erlotinib in combination with tipifarnib. Methods: Patients with advanced solid tumors received escalating doses of erlotinib (once daily orally) and tipifarnib (bid orally on days 1–21) on a 28-day cycle. The dose-limiting toxicity (DLT) was defined as cycle 1 grade 4 ANC > 5 days, grade 4 thrombocytompenia, serum cr. > 2x baseline, grade 3+ vomiting, diarrhea, skin rash despite maximal support or other non-heme toxicities. Results: To date, 12 patients (9F/3M, median age 49) have been treated through 4 dose levels as shown below. Nine patients, treated at dose levels 1 to 3, have received 20 cycles of treatment and are evaluable for toxicities. Three patients have just began treatment at dose level 4, the reported MTD for single agents, and are not yet evaluable for toxicity. No DLTs have been observed. Grade 2+ treatment related toxicities in all cycles of treatment include rash (15% grade 2), diarrhea (5% grade 2, 5% grade 3), fatigue (10% grade 2), and abnormal LFTs(10% grade 2). No objective response has been observed. Four patients have stable disease for at least 2 months. Additional patients will be enrolled at the recommended phase II dose, which is anticipated to be dose level 4, for further evaluation of dose and adverse events relationship, PK and markers of FT and EGFR inhibition, results of which will be presented. Conclusions: The combination of erlotinib and tipifarnib is well tolerated. The expected phase II doses to be recommended are erlotinib at 150mg once daily and tipifarnib at 300mg bid. No significant financial relationships to disclose.