tbuckley/cabot-search huggingface dataset:
Cost-benefit of recurrence score–guided treatment using an Onco<i>type</i> DX 21-gene assay: A single institution analysis.
Authors: Kamal Kant Singh Abbi, Nauman Shahid, Muhammad Khurram Hameed, Brian Fink, Colette Gaba, Iman Mohamed
Journal: Journal of Clinical Oncology (2013)

29 Background: In 2010 the National Comprehensive Cancer Network recommended a 21-gene assay recurrence score (RS) to aid in the adjuvant treatment decision among patients with estrogen receptor positive, lymph node negative early stage breast cancer. Early-decision impact studies show that the RS can reduce overall chemotherapy use by 27%. This study was performed to assess the cost-benefit of the test for the patients diagnosed and treated an academic institute before 2010. Methods: Data from early breast cancer estrogen-receptor–positive and lymph-node–negative patients (n = 87), who were diagnosed and treated at our center from 2004-2010 were analyzed. All patients had the 21-gene recurrence test done to guide in their management. Cost of chemotherapy, adverse effects, and supportive care costs were calculated from previously published articles. Results: 66 patients with stage I breast cancer and 21 patients with stage II were analyzed. All but one patient had a tumor size more than 5mm. In total, 27 patients received chemotherapy. Characteristics of patients receiving chemotherapy are shown in the table. Cost of 21 gene recurrence score assay was $4,000. Savings for each patient who did not receive chemotherapy was $21,715 after accounting for cost of the test. The total savings for 60 patients who did not receive chemotherapy was $1,302,900. Conclusions: Use of the 21-gene assay in patients with early stage lymph node negative breast cancer improves health outcomes by avoiding chemotherapy-related adverse events. It also appears to add no incremental costs. This study emphasizes the cost-saving potential of the Oncotype Dx 21 gene assay. [Table: see text]
Early tumor shrinkage and long-term outcome in metastatic colorectal cancer (mCRC): Assessment of predictive utility across treatment arms in the CRYSTAL and OPUS studies.
Authors: H. Piessevaux, E. Van Cutsem, C. Bokemeyer, M. Schlichting, S. Heeger, S. Tejpar
Journal: Journal of Clinical Oncology (2011)

3572 Background: The relationship between tumor radiological (RX) response and long-term outcome is unclear for current drugs. Early response is a proposed efficacy endpoint for drug screening and on-treatment evaluation and warrants investigation as a predictor of long-term outcomes. We previously showed early tumor shrinkage (ETS) in combination chemotherapy (CT) + cetuximab (cet) regimens identified KRAS wild-type (wt) mCRC patients (pts) with improved outcome. We used the CRYSTAL and OPUS studies to quantify the predictive power of tumor size changes at week (wk) 8 for long-term outcome investigating heterogeneity across treatment arms (CT or CT + cet). Methods: Tumor KRAS status and RX data at wk 8 were available for 820 pts from the CRYSTAL study and 297 from the OPUS study. Using investigators' assessments, a relative change in the sum of the longest diameters of target lesions compared to baseline was calculated. Time-Dependent Receiver-Operating-Characteristics (TDROC) were used to obtain Cτ indices. Cox regression models and Subpopulation Treatment Effect Pattern Plots (STEPP) identified interaction between ETS and treatment arm. Outcome measures were progression-free survival (PFS) and overall survival (OS). Results: In both studies TDROC indicated a strong relationship between change in tumor size at wk 8 and PFS in KRAS wt mCRC pts receiving CT + cet. This was weaker in the CT arm. Data were similar for OS with lower Cτ indices. Treatment interaction was confirmed by significant interaction terms for PFS in the Cox regression models and for both PFS and OS with STEPP methodology. Conclusions: These findings demonstrate a strong relationship between ETS and long-term outcome in KRAS wt mCRC pts receiving CT + cet compared with CT alone. This suggests a possible use for ETS as a predictor of outcome in this setting. Further studies are needed to see how this may impact on clinical decision making. CRYSTAL OPUS Cτ Cox (p value) STEPP (p value) Cτ Cox (p value) STEPP (p value) PFS KRAS wt/CT 0.604 0.020 0.048 0.547 0.004 0.053 KRAS wt/CT + cet 0.688 0.703 OS KRAS wt/CT 0.553 0.100 0.001 0.566 0.114 0.036 KRAS wt/CT + cet 0.606 0.655
Population-based comparison of surgical margin status for robotic versus open radical prostatectomy.
Authors: Jim C. Hu, Giorgio Gandaglia, Paul Linh Nguyen, Quoc-Dien Trinh, Ya-Chen T. Shih, Firas Abdollah, Karim Chamie, Jonathan L. Wright, Pierre I. Karakiewicz, Maxine Sun
Journal: Journal of Clinical Oncology (2014)

51 Background: Robotic-assisted radical prostatectomy (RARP) remains controversial due to exaggerated marketing claims, higher costs, hidden risks, and few clinically significant benefits, including an absence of improved cancer control compared to open radical prostatectomy (ORP). The purpose of our study is to compare surgical margin status by surgical approach. Methods: We identified 13,434 men with a histologically confirmed, non-metastatic prostate cancer treated with RARP versus ORP during 2004 and 2009 from Surveillance, Epidemiology, and End Results (SEER)–Medicare linked data. Propensity-based analyses were performed to minimize treatment selection biases. Generalized linear regression models were computed for comparison of radical prostatectomy surgical margin status by surgical approach. Results: During the study period, 5,556 and 7,878 men underwent RARP and ORP, respectively. In the propensity-adjusted cohort, the incidence of positive surgical margins was significantly lower among men undergoing RARP versus ORP (13.7% vs. 18.4%, odds ratio [OR]: 0.68, 95% confidence interval [CI]: 0.63–0.73, p&lt;0.001). This reduction in the incidence of positive surgical margins of RARP over ORP was more pronounced among men with more advanced disease—6.6% lower absolute incidence of positive margins among men with intermediate- and high-risk disease (p&lt;0.001, respectively) and 15.4% lower absolute incidence of positive margins among men with extracapsular extension (p&lt;0.001). Moreover, RARP was associated with lower odds of positive surgical margins compared to ORP for pT2 (Odds Ratio [OR] 0.67, 95% Confidence Interval [CI] 0.61–0.74, p&lt;0.001) and pT3a (OR 0.72, 95% CI 0.60–0.85, p&lt;0.001) disease. Additionally, RARP was associated with lower odds of positive surgical margins for intermediate (OR 0.66, 95% CI 0.58–0.74) and high-risk (OR 0.69, 95% CI 0.64–0.75) disease. Conclusions: RARP was associated with improved surgical margin status among men with intermediate and high-risk disease. This has important implications for cancer control, patient quality of life, health care delivery and additional costs of downstream therapies.
Impact of body mass index on clinicopathologic outcome and biochemical recurrence after radical prostatectomy in 1,257 Japanese patients with prostate cancer.
Authors: Shintaro Narita, Koji Mitsuzuka, Takahiro Yoneyama, Sadafumi Kawamura, Yoichi Arai, Chikara Ohyama, Tatsuo Tochigi, Takuhiro Yamaguchi, Tomonori Habuchi
Journal: Journal of Clinical Oncology (2013)

176 Background: To determine the impact of body mass index (BMI) on the clinicopathological characteristics and biochemical recurrence of prostate cancer (PCa) after radical prostatectomy (RP) in Japanese men. Methods: The medical records of 1,257 men with PCa treated by radical prostatectomy without neoadjuvant therapy at four medical centers between 2001 and 2009 were retrospectively reviewed. Patients were categorized into four groups using the WHO BMI classification and recommended BMI quartiles. Associations of the various BMI categories with clinicopathological characteristics and biochemical recurrences were statistically evaluated. Biochemical recurrence was defined as a prostate specific antigen (PSA) level of &gt;0.2 ng/ml. Results: Of the 1,257 patients, 230 (18.1%) experienced biochemical recurrence during the median follow-up period of 49 months. The median BMI was 23.8 kg/m 2 , and 1.4% patients were underweight, 65.4% were of normal weight, 30.9% were overweight, and 2.4% were obese (WHO classification). Preoperative PSA levels and PSA density (PSAD) were significantly higher in the underweight group than in the other groups. Pathological characteristics did not differ significantly among BMI categories. As per the WHO classification and quartile categories, biochemical recurrence rate was comparable among the BMI groups. After adjusting for other pre- and perioperative covariables, multivariate Cox proportional hazards analysis revealed that a high BMI did not have an independent impact on biochemical recurrence-free survival. Conclusions: Underweight Japanese PCa patients who underwent radical prostatectomy had higher preoperative PSA levels and PSAD. However, high BMI was not associated with increased biochemical recurrence rate.
Trends in hospital and office-based chemotherapy administration 2005-2012 for Medicare and commercially insured patients.
Authors: Kathleen A. Foley, Rebecca Bechhold
Journal: Journal of Clinical Oncology (2013)

274 Background: The 2013 Community Oncology Practice Impact Report notes an increase of 20% in the number of community clinics closing since 2011. The objective of this study was to examine trends in location and reimbursement of chemotherapy in office-based (OBS) and outpatient hospital settings (OHS). Methods: Using the MarketScan Research Databases, first administrations of bevacizumab and trastuzumab were identified from 1/1/2005 through 12/31/2012 for patients with commercial or employer-sponsored supplemental Medicare insurance. Bevacizumab claims were excluded if the claim had a diagnosis related to macular degeneration or other eye disease. Claims for both drugs were excluded if the reimbursed amount was less than $100. Chemotherapy administration reimbursements were identified through CPT codes on the same day as the day as the drug charge. All claims were identified as occurring in OB or OHS. Results: The percent of bevacizumab claims occurring in OHS increased from 6 to 34% among Medicare claims, and from 15 to 42% among commercial claims from 2005 to 2012. For trastuzumab, the increases were 4 to 35%, and 10 to 35% in Medicare and commercial claims, respectively. OHS reimbursements were consistently higher than OBS reimbursements for chemotherapy administration and drug for both drugs across both payers. Conclusions: Although the differential in reimbursements between OHS and OBS declined in the most recent two years, OHS reimbursements remained substantially higher while the shift in chemotherapy administration from OBS to OHS has continued through 2012. Continued attention to reimbursement differences between OHS and OBS is warranted and additional research is needed to more fully document the impact on patients, providers, and payers. [Table: see text]
Impact on stage distribution of gastric cancer by the National Cancer Screening Program (NCSP) in Korea.
Authors: J. K. Jun, K. S. Choi, H. Lee, E. Park
Journal: Journal of Clinical Oncology (2011)

1579 Background: Gastric cancer screening started in 1999 as a part of the National Cancer Screening Program (NCSP) in Korea. The aim of this study was to investigate whether downstaging of gastric cancer occurred in the NCSP. Methods: A case-control study was performed to compare the staging of gastric cancer diagnosed in the NCSP-screened population with cancer clinically diagnosed in non-attendants of NCSP. Among the target population of NCSP in 2006, a total of 6,692 incident gastric cancer cases and same controls were matched according to age, gender, and socioeconomic status. Using conditional logistic regression model, the odds ratio (OR) for early stage (localized in the SEER summary stage) gastric cancer were estimated. Results: Proportions of NCSP-screened cases by stages were 54.7% (localized), 23.1% (regional), 7.7% (distant) and 14.5% (unknown), and those of controls were 41.8%, 29.5%, 12.6%, and 16.1%, respectively. The OR for early stage cancer according to gastric cancer screening were 1.71 (95% CI == 1.59-1.84). Conclusions: This study demonstrates significant downstaging of gastric cancer in the NCSP-screened population. It provides strong evidence for the effectiveness of the National Cancer Screening Program in Korea.
A phase I study of ganetespib in advanced hepatocellular carcinoma (HCC).
Authors: Lipika Goyal, Raymond Couric Wadlow, Lawrence Scott Blaszkowsky, Brian M. Wolpin, Eamala Vasudev, Susan Sheehan, Michelle Knowles, Andrew X. Zhu
Journal: Journal of Clinical Oncology (2013)

259 Background: Ganetespib is an Hsp90 inhibitor that downregulates EGFR, VEGFR, HER2, MET, IGF-IR, and other Hsp90 client proteins involved in hepatocarcinogenesis, thereby making it an attractive therapy for HCC. This multicenter Phase I study was performed to establish the safety, tolerability, recommended Phase 2 dose (RP2D), and preliminary activity of ganetespib in patients with advanced HCC. Methods: Thirteen patients with advanced HCC, Child-Pugh A or B cirrhosis, progression on or intolerance to sorafenib, and ECOG PS ≤ 1 were enrolled in a standard 3x3 dose escalation study at ganetespib doses of 100 mg/m 2 , 150 mg/m 2 , and 200 mg/m 2 IV given on days 1, 8, and 15 of a 28 day cycle. RECIST 1.1 response was evaluated by CT/MRI every 8 weeks. The primary objective was to determine the RP2D, and secondary objectives included assessments of safety, toxicity, pharmacokinetics, median time to progression (TTP), median progression-free survival (PFS), median overall survival (OS), and objective response rate (ORR). Results: Twelve of the 13 patients enrolled received study drug, and enrollment is ongoing for the 200 mg/m 2 cohort. Of the 12 patients: male 66%; median age 57 years; median number of prior treatments 2; Asian 33%; HCC etiology (HBV 41.7%, HCV 41.7%, hemachromatosis 8.3%, unknown 16.7%); median baseline AFP 115.3 ng/mL. Median TTP for the 10 evaluable patients was 49 days (1.6 months). No responses were seen, but 2/10 (20.0%) patients had stable disease at 8 weeks. AFP response, defined as reduction from baseline of &gt;50% in patients with an elevated baseline AFP, was seen in 0% of patients. Most common AEs: diarrhea (100%), AST elevation (58.3%), hyperglycemia (58.3%), and fatigue (58.3%). Most common Gr 3/4 AEs: hyperglycemia (25%), anemia (16.7%), lipasemia (16.7%), and ALKP elevation (16.7%). One (8.3%) patient had a fatal AE, septic shock, within 30 days of receiving the drug. One DLT was observed: Gr 3 lipasemia at the 100mg/m 2 dose. Conclusions: Ganetespib had a manageable safety profile and demonstrated limited efficacy in patients with advanced HCC. Determination of the R2PD, further assessment of clinical efficacy, and analysis of molecular markers are still pending, and a follow-up Phase II study will be considered based on this data. Clinical trial information: NCT01665937.
TTBK2 circular RNA promotes glioma malignancy by regulating miR-217/HNF1β/Derlin-1 pathway
Authors: Jian Zheng, Xiaobai Liu, Yixue Xue, Wei Gong, Jun Ma, Zhuo Xi, Zhongyou Que, Yunhui Liu
Journal: Journal of Hematology & Oncology (2017)

Circular RNAs are a subgroup of non-coding RNAs and generated by a mammalian genome. Herein, the expression and function of circular RNA circ-TTBK2 were investigated in human glioma cells.Fluorescence in situ hybridization and quantitative real-time PCR were conducted to profile the cell distribution and expression of circ-TTBK2 and microRNA-217 (miR-217) in glioma tissues and cells. Immunohistochemical and western blot were used to determine the expression of HNF1β and Derlin-1 in glioma tissues and cells. Stable knockdown of circ-TTBK2 or overexpression of miR-217 glioma cell lines (U87 and U251) were established to explore the function of circ-TTBK2 and miR-217 in glioma cells. Further, luciferase reports and RNA immunoprecipitation were used to investigate the correlation between circ-TTBK2 and miR-217. Cell Counting Kit-8, transwell assays, and flow cytometry were used to investigate circ-TTBK2 and miR-217 function including cell proliferation, migration and invasion, and apoptosis, respectively. ChIP assays were used to ascertain the correlations between HNF1β and Derlin-1.We found that circ-TTBK2 was upregulated in glioma tissues and cell lines, while linear TTBK2 was not dysregulated in glioma tissues and cells. Enhanced expression of circ-TTBK2 promoted cell proliferation, migration, and invasion, while inhibited apoptosis. MiR-217 was downregulated in glioma tissues and cell lines. We also found that circ-TTBK2, but not linear TTBK2, acted as miR-217 sponge in a sequence-specific manner. In addition, upregulated circ-TTBK2 decreased miR-217 expression and there was a reciprocal negative feedback between them in an Argonaute2-dependent manner. Moreover, reintroduction of miR-217 significantly reversed circ-TTBK2-mediated promotion of glioma progression. HNF1β was a direct target of miR-217, and played oncogenic role in glioma cells. Remarkably, circ-TTBK2 knockdown combined with miR-217 overexpression led to tumor regression in vivo.These results demonstrated a novel role circ-TTBK2 in the glioma progression.
Effectiveness of HCC treatments in real-world experiences.
Authors: Glen I. Misek, Mark Keckeisen, Venkata K Jayanti
Journal: Journal of Clinical Oncology (2012)

61 Background: The global incidence of HCC is over 700,000 patients making it the sixth leading cancer. Recently new drugs have been approved to treat HCC. Nevertheless, prognosis is poor with a 5 year survival of 11%. Hence, it is important to understand if there are differences in OS in the Real World (RWE) based on patient demographics, comorbidities and whether current treatments are effective. Methods: A robust global database of HCC patients was constructed from patient chart data with nearly 4,000 unique patient records from the United States, the European Union, and Asia in 2011. Several hypotheses were tested including the impact of ethnicity, presence of Hep B or C or cirrhosis, stage at diagnosis and/or if current treatments used could predict PFS and /or OS. CART and CHAID analyses were conducted to help determine patient segments and treatment flows in conjunction with Kaplan-Meier plots to understand the differences in survival based key patient and treatment attributes. Results: One year survival appears to be associated with geography as it is significantly lower in China/ Korea compared to the United States and the European Union. Significantly higher one year survival rates are observed for HCC patients in the European Union and the United States receiving TACE compared with patients receiving sorafenib first line. However, in Asia there are no differences. Across all three regions sorafenib use does not effect OS in Stage IV patients. Further, no significant differences in one year survival are seen in patients with Hep C or B or cirrhosis compared to those with no history of liver disease. Sorafenib treatment duration in China appears to be substantially lower. Finally, Child-Pugh C patients had lower survival compared to Child-Pugh A or B patients. Conclusions: Early diagnosis, intervention and treatment of HCC appear to be important predictors of survival. Stratifying groups by type of drug treatment including sorafenib use does not appear to have a measurable effect on OS. Efforts aimed towards screening, early detection and treatment initiation during early stages to improve RWE for HCC patients may be more effective than expanding treatment with sorafenib in late stage patients. Given the lack of significance in OS for late stage patients treated with sorafenib across the globe, serious thought should be given its use for late stage patients.
Clinical efficacy of adjuvant surgery following systemic treatments in patients with initially unresectable pancreatic cancer: Results of a project study for pancreatic surgery by the Japanese Society of Hepato-Biliary-Pancreatic Surgery.
Authors: Satoshi Hirano, Sohei Satoi, Hiroki Yamaue, Kentaro Kato, Shinichiro Takahashi, Seiko Hirono, Shin Takeda, Hidetoshi Eguchi, Masayuki Sho, Keita Wada, Hiroyuki Shinchi, A-Hon Kwon, Taira Kinoshita, Akimasa Nakao, Hiroaki Nagano, Yoshiyuki Nakajima, Keiji Sano, Masaru Miyazaki, Tadahiro Takada
Journal: Journal of Clinical Oncology (2013)

255 Background: Medical oncologists or pancreatic surgeons have identified candidates for surgical resection in patients with initially unresectable pancreatic cancer who favorably responded to multimodal treatment. Additional surgical resection during multimodal treatment, is called “adjuvant surgery”. A multicenter survey was conducted to explore the clinical efficacy of adjuvant surgery for initially unresectable pancreatic cancer with a long-term favorable response to systemic treatments. Methods: Clinical data, including the primary endpoint of overall survival were retrospectively compared between 58 initially unresectable pancreatic cancer patients that underwent adjuvant surgery with a favorable response to non-surgical cancer treatments over 6 months after the initial treatment (adjuvant surgery group) and 101 patients who did not undergo adjuvant surgery (control group). Results: The median observation periods were 51 months (20-122) in the control group, and 54 months (26-125) in the adjuvant surgery group, respectively. The actuarial survival rate at 1, 3, and 5 years after initial treatment in adjuvant surgery group (95, 53, and 34%) was significantly better than that in control group (88, 18, and 10%, p&lt;0.0001). The propensity score analysis to provide adjustment of significant differences in the clinical backgrounds between the two groups revealed that adjuvant surgery was a significant independent prognostic variable with an adjusted hazard ratio (95% confidential interval) of 0.569 (0.36-0.89). Subgroup analysis according to the time from initial treatment to surgical resection showed a significant favorable difference in the overall survival in patients who underwent adjuvant surgery over 240 days after the initial treatment. Conclusions: The adjuvant surgery can occupy an important position in the multimodal therapy for patients with initially unresectable pancreatic cancer. The overall survival rate from the initial treatment is extremely high, especially in patients who received systemic treatments for more than 240 days.