tbuckley/cabot-search huggingface dataset:
Limits on costs and values of anticancer drugs in metastatic colorectal cancer: Policies and proposal.
Authors: Helmy M. Guirgis
Journal: Journal of Clinical Oncology (2016)

607 Background: Guidelines from the National Institute of Health and Clinical Excellence (NICE) in the United Kingdom (UK) set limits on cost-effectiveness ratios (ACER) of 20,000-30,000 pound per quality of life-year gained (QALY). Bevacizumab (Bev) is not approved in UK in 1 st -line metastatic colorectal cancer (mCRC). The objectives were twofold:1- Propose limits of 5,000 in Unites Sates dollars (US$) on 4-week drug costs and values 2- Weigh and compare drugs in various lines of mCRC. Methods: The 4-week costs (4wC) were calculated. Values were expressed as 4wC x hazard ratio of death (HR). Relative values (RV) were computed as 5,000/values. Results: In 1 st -line, 4wC of Bev (5.0mg/Kg) was $4,620, values 3,049 and RV 1.64. Panitumumab (Pan) were $8,223, values 6,833 and RV 0.73 Cetuximab (Cet) were $9,775, values 7,820 and RV 0.64. In 2 nd- line, 4wC of Aflibercept (Afl) was $5,000, RV 1.22, Bev (10 mg/KG) $9,240, RV 0.72 and Ramucirumab (Ram) $11,200 with RV 0.53. Regorafenib (Reg) in refractory disease had 4wC of $9,400, value 7,238 and RV 0.69. Trifluridine/tipiracil (TAS 102) at projected costs of $5,000 to $9,000, values were estimated at 3,400 to 6,120 with RV of 1.47 to 0.82. Conclusions: In 1 st -line Bev had lower 4wC with higher values and RV than Pan, Cet and the $5,000 proposed limits. In 2 nd- line, Afl was at the borderline of limits. Costs of Pan, Cet, Ram and Bev in 2 nd and Reg in refractory disease were excessive and inflated for their values. Preliminary cost evaluation of TAS 102 seemed promising.
Common genetic variants in the immunoglobulin heavy chain locus and their differential impact on group A streptococcal disease susceptibility: a comparative meta-analysis of genetic susceptibility studies
Authors: Tom Parks, Kathryn Auckland, Anna Rautanen, Corey Watson, Mariana M Mirabel, Joseph Kado, John K Kauwe, Theresa L Lamagni, Alexander J Mentzer, Shiranee Sriskandan, Matthew Thomas, Stephen Chapman, Malcolm Brodlie, Andrew J Pollard, Julien Colot, J Anthony G Scott, Thomas N Williams, Andrew C Steer, Adrian V S Hill
Journal: The Lancet (2017)
A phase II trial of chemoradiation (CR) for organ preservation in resectable stage III or IV squamous cell carcinomas of the larynx (L) or oropharynx (OP): A trial of the Eastern Cooperative Oncology Group (E2399)
Authors: A. J. Cmelak, S. Li, M. Goldwasser, B. A. Murphy, G. L. Adams, M. Cannon, H. Pinto, D. Rosenthal, A. Forastiere
Journal: Journal of Clinical Oncology (2005)

5509 Background: Concurrent cisplatin and radiation (RT) for locally-advanced larynx cancer provides higer organ preservation rates than either RT alone or sequential treatment. As local control rates improve, distant metastases have become a major failure pattern. This phase II trial evaluates taxane-based induction chemotherapy followed by CR for organ preservation in both resectable AJCC stage II/IV L and OP patients. Methods: Pts require biopsy-proven squamous cell histology, AJCC stage III/IV resectable disease (T2N+, or T3-T4N0–3M0), age≥18, PS 0–2, good organ function, and no prior chemotherapy or radiation. Induction included paclitaxel (P) 175mg/m2, carboplatin (C) AUC 6 for 2 cycles 21 days apart, along with epoetin (Epo) 40kU weekly if Hgb≤15 (male) or ≤14 (female). If no tumor progression was seen, pts went on to CR: (P) 30mg/m2 with radiation 70Gy/7 wks with continued Epo (if needed). QOL, speech and swallowing assessments were done at baseline and after treatment. Results: 107 pts, excluding 4 for ineligibility (70 OP, 37 L) are evaluable for early efficacy and all patients were evaluable for toxicity evaluation. Median FU is 24 months. Male=88, Female=19, ages 24–86 (med 58), ECOG PS 0=50, PS1=52, PS2=5. 12 pts had >10% weight loss before treatment. 98% completed both cycles of induction (7% received dose reduction of ≥25% on second cycle). The best response at primary site is CR=27%, PR=23%, stable=19%, PD=7%, unknown=24%. Objective responses were slightly higher in the OP pts (56%) than L pts (39%) (p=0.15). 2 patients received no chemo during radiation due to toxicity. 91% received ≥5/7 weekly doses of P during CR and 94% completed radiation. 14% required PEG tubes before or during treatment. Pts with grade 3/4 toxicities include: allergy 2pts/1pt, neutropenia 15/37, F/N 6/1, weight loss 7/0, skin 13/2, mucositis 47/7, N/V 10/3. There were no grade 5 toxicities and 1 pulm embolus. Conclusions: This regimen is well tolerated with high rates of chemo and radiation delivery. Longer FU is required to determine 1-year organ preservation rate, long-term toxicities, speech/swallowing function, and QOL. No significant financial relationships to disclose.
Prognostic impact of p53 compared to CEA and CA 19-9 in resectable colorectal cancer
Authors: A. M. Waaga-Gasser, C. Gerstlauer, M. Bueter, M. Grimm, U. Maeder, A. Thalheimer, A. Trumpfheller, A. Thiede, H.-J. Gassel, D. Meyer, M. Gasser
Journal: Journal of Clinical Oncology (2005)

3541 Background: Colorectal cancer (CRC) is a major cause of cancer-related deaths in the western world. This study was carried out to evaluate the prognostic significance of p53 compared to CEA and CA 19-9 in order to predict the risk of tumor recurrence. Methods: 783 patients from our center with confirmed CRC were evaluated retrospectively. The collective included only R0-resected stage I-III patients, those patients with metastases or a second carcinoma were excluded. Sex, age, location of the tumor, UICC stage with level of wall infiltration plus lymph node metastases, grading, CEA CA 19-9 and p53 were analyzed to determine the predictive value of the molecular markers (Kaplan-Meier, Chi-Quadrat-test). Preoperative blood samples were analyzed by Luminex (CEA and CA 19-9) and ELISA (p53). In addition, tumor specimens were assessed immunohistologically and by Real Time PCR. Results: Preoperative CEA levels were significantly associated with staging (p=0,002), level of wall infiltaration (p<0,001) as well as with lymph node metastases (p=0,03). Tumor free survival and relapse free time were also significantly influenced by UICC staging (p<0,0001), level of wall infiltration (p<0,0001), lymph node metastases (p<0,0001), and CEA (p=0,0003 vs p=0,0436). Stage III patients with a CEA level <5 ng/ml had a significantly higher survival than those with values >5 ng/ml (p=0,0044); interestingly, a better prognosis was observed in patients of UICC IIIA (p=0,0410). Furthermore, patients with colon cancer showed a lower relapse rate than those of the rectum (p=0,021). No predictive significance was observed for CA 19-9 and p53 (serum). In contrast, the expression of CA-19-9 and p53 as well as CEA in the tumor was dependent on the stage of the patients (CEA: UICC I/II 55,5%, III 100%; CA 19-9: UICC I/II 37,5%, III 80%; p53: UICC I/II 37,1%, III 57,1%) and combined with worse prognosis. Conclusions: This study suggests that preoperative CEA level combined with CA 19-9 and additional p53 in the tumor are suitable markers for stage III colorectal cancer patients, indicating that these patients should be considred as high risk group. Patients with a high score for p53, CEA, and CA 19-9 in this group may be the best candidates for an aggressive adjuvant therapy. No significant financial relationships to disclose.
Dependence of intrafraction prostate motion within the pelvis on fraction duration during whole pelvic intensity modulated arctherapy (IMAT) versus dynamic IMRT.
Authors: Nicolas Lescut, Etienne Martin, Philippe Maingon, Magali Quivrin, Celine Mirjolet, Suzanne Naudy, Aurelie Petitfils, Gilles Crehange
Journal: Journal of Clinical Oncology (2013)

190 Background: To compare the 3-dimensional intra-fraction variations of prostate position within the pelvis with whole-pelvic fixed-field intensity-modulated radiation therapy (IMRT) vs. intensity-modulated arc therapy (IMAT) in high-risk prostate cancer. Methods: Fifteen PCa patients underwent whole pelvic radiotherapy using either dynamic IMRT with a sliding window technique (n= 8) or IMAT (n= 7). All the patients had a kV cone-beam computed tomography (CBCT) before and immediately after each fraction of IMRT or IMAT. Intra-fraction motions of the prostate were determined using a 2-step procedure performed on each pre- and post-treatment imaging: 1) planning CT and CBCT were matched on bony structures after automatic semi-rigid fusion alongside the 3 axis (x, y, z), 2) planning CT and CBCT were matched on the prostate with respect to intra-prostatic markers: x soft , y soft , z soft . The position of the prostate within the pelvis for each pre- and post-treatment study points was defined as x pros = (x bone – x soft ), y pros = (y bone – y soft ) and z pros = (z bone – z soft ). Rectum and bladder were outlined on each CBCT with the aim to assess changes in rectal or vesical repletion during each fraction. Organ distension was assessed by measuring the average rectal cross-sectional area (rCSA; defined as the rectal volume divided by length), and the area of the bladder when evaluated 2.5cm above the prostate base (A-blad) on pre- and post-treatment CBCT. Results: Two hundred and ninety four CBCT were reviewed for this analysis. The average fraction duration was shorter with IMAT than with IMRT (4’49’’, vs. 11’00’’, p&lt; 0.001). During fractions of IMRT the prostate showed statistically significant shifts in the longitudinal (p= 0,049) and lateral (p=0,013) axis while it was not statistically significant during fractions of IMAT. Intra-fraction rCSA increased neither during IMAT nor IMRT whereas A-blad increased only during fractions of IMRT but with no correlation with prostate displacements. Conclusions: The prostate moves within the pelvis during an IMRT course which could lead to a greater daily geographic miss when compared to the IMAT technique.
Measuring adverse event rates in oncology inpatients using trigger tools: An assessment of measurement properties.
Authors: Thea Otto Mattsson, Kim Brixen, Janne Lehmann Knudsen, Jorn Herrstedt
Journal: Journal of Clinical Oncology (2012)

235 Background: The Institute for Healthcare Improvement developed the Global Trigger Tool (GTT) for measuring harm rates over time in 2006. Few studies have been published on the measurement properties of GTT and no studies have assessed the value of adding specific modules to the generic GTT. We, therefore, aimed to determine inter-rater reliability, and to evaluate the effect of interrater variation on the reliability of the generic GTT to detect adverse event rates over time. Furthermore to evaluate the effect of adding an oncology specific module to the generic GTT on number and category of adverse events (AEs) identified. Methods: A retrospective chart review was performed by two teams consisting of two primary reviewers. One team used the general GTT, and the other used an oncology specific GTT (GTTO); consisting of the general GTT module plus an additional oncology module. A random sample of 10 charts was selected every two weeks between all discharged patients from a Department of Oncology in 2010. n=240. All charts were reviewed by both teams using standard GTT methods and measures. AEs per 1,000 admission days and AEs per 100 admissions where used to draw Statistical process control (SPC) charts for evaluation of the patient safety process. Inter-rater variability between review teams was assessed calculating the Kappa Cohen coefficient using data from the identical general GTT module. Results: Reliability between the two teams of reviewers to identify an AE was moderate [K=0.45]. A comparison of SPC charts, using the results from the identical general module, showed that moderate agreement gave rise to different conclusions on the patient safety process between teams. Comparing GTT with GTTO we found no significant difference (CI 95% [0.06-0.08]) in number of identified AEs and an equal distribution of the events on harm categories. GTT and GTTO identified 56 and 57 AEs respectively. Conclusions: Moderate agreement between review teams gave rise to different conclusions on the patient safety process suggesting limited use of the GTT to track harm rates over time. Addition of an oncology specific module showed no significant effect on the total number or distribution of AEs on harm categories.
Reducing time to initiation of colon cancer adjuvant chemotherapy in a large community-based hospital.
Authors: Karen Bochert, Brian Rentschler, Chris Powers, Frederick Slezak, Sameer A. Mahesh
Journal: Journal of Clinical Oncology (2012)

125 Background: Chemotherapy is standard of care after definitive surgery for stage III and certain subsets of stage II colon cancer (CC). A recent meta-analysis showed that for every 4 week delay in administering adjuvant chemotherapy relative survival decreases by 15%. At our institution, 24% of patients undergoing colon cancer surgery in 2010 subsequently received chemotherapy. On average, this process took 41 days from date of discharge to first chemotherapy (range 12-166 days). We sought to decrease this time to an average of 28 days. Methods: Previously, starting adjuvant chemotherapy was a step-wise process starting from the surgeon’s post operative visit to the medical oncologist’s office visit followed by port placement and finally, the commencement of chemotherapy. We instituted a program of concurrent scheduling of appointments by the colorectal cancer navigator (CRCN) upon availability of the pathology report. Primary end-point was time to start of chemotherapy from day of discharge (TTCD). Results: Twenty-three patients were eligible since inception of the program in September 2011. Of these, 5 declined entry and 2 were under the care of non-participating physicians, hence excluded from analysis. TTCD before and after implementation of the program are shown in the table. Two patients required financial assistance for capecitabine (C) that delayed TTCD to &gt; 4 weeks. Results are shown after excluding those patients as well. Conclusions: Utilizing the CRCN to coordinate appointments for patients who required adjuvant chemotherapy significantly decreased the TTCD which might translate into better CC outcomes. [Table: see text]
Financial risk-sharing agreements: Using options to make marginal benefits cost effective.
Authors: Henry Jacob Conter
Journal: Journal of Clinical Oncology (2016)

41 Background: New cancer treatments have become increasingly costly. Although new drugs may be sufficiently cost-efficiency for a primary indication (i1) to receive funding, subsequent indications (ia) may not prove cost-effective. A financial risk-sharing agreement to increase access is proposed. A potential 2012 real-world implementation in Canada for pazopanib use in metastatic renal cell carcinoma (mRCC) as i1, and soft-tissue sarcoma (STS) as ia is presented. Methods: The market value of an indication can be approximated by its net-present-value (NPV) of expected cash flows. If the incremental cost-effectiveness ratio (ICER) for ia is expected to be greater than willingness-to-pay (WTP), the payer then has an incentive to enter into a risk-sharing agreement. A binomial option pricing model is employed to compute the price of the call option to contract such an agreement. The probability of being eligible for ia is extracted from the pan-Canadian Oncology Drug Review (pCODR), a national drug funding advisory body. Correspondence with industry was performed to identify additional ia. Cost, effectiveness, the ICER, discount rates, and drug revenues are calculated using inputs from pCODR, the Bank of Canada, Statistics Canada, and pazopanib’s relevant clinical data at the time of its submission for i1. Results: Of the 47 drugs eligible for i1, 46% are eligible for an ia(Wilson interval 33%-60%). For pazopanib in mRCC, at a mean price of $164/day and an ICER of $0-$57,309, the expected NPV was computed to be $338M. In STS, based on its clinical data at the time, at the same price, the ICER was expected to be &gt; $100,000, with an NPV of $37M. The price of the call option is $17M. Alternatively, the price of pazopanib could be adjusted to $172/day in mRCC, keeping its ICER below WTP, with an agreement that if efficacious, the drug would be provided by the company gratis for STS patients. Conclusions: In a reality where high drug costs are limiting access for vulnerable patients, risk sharing agreements using financial instruments offer an opportunity to re-deploy health technology assessment to expand drug access. For a price increase of $8 per day in i1, Canadian STS patients could have had access to an effective treatment instead of nothing.
Linking commercial claims and state registry data to assess cancer care quality at the medical group level: Early lessons from California.
Authors: Ann Woo, Kathleen A. Foley
Journal: Journal of Clinical Oncology (2014)

269 Background: The Integrated Healthcare Association (IHA) is a non-profit organization which runs the largest Pay for Performance program in California. We describe a feasibility study to apply NQF cancer quality measures to linked commercial claims and state registry data and calculate results at the physician organization level. We describe phase I of the study: identifying appropriate measures and securing access to the data. Methods: We requested technical specifications for 9 NQF breast and colon cancer quality measures from the measure stewards and 2009 –2012 claims data from 7 California health plans. Results: Two barriers were identified in phase I: First, California Cancer Registry (CCR) data policies, designed for public health surveillance and not quality measurement, caused delays and present hurdles to public reporting. CCR data is not available until it is at least 95% complete, so 2011 data was not available until October 2013. Moreover, CCR requires that they conduct the data linkage, which required new data use agreements between the data aggregator and each participating insurer – costly in both time and legal fees. Finally, obstacles to public reporting any of the CCR data at the provider level still exist. Barrier 2: NQF measure specifications for linked claims-registry data sets do not currently exist, so the project team developed them, adding to the problem of proliferating non-harmonized quality measures. Conclusions: While the application of NQF measures to claims-registry linkage appears feasible for measurement of cancer care quality at the medical group level, registry policies and the lack of standard technical specifications for linked claims-registry data sets adversely impact the timeliness, usability, and comparability of results using two widely available data sources. More flexible policies on the part of data registries and attention to measure harmonization could improve data quality and usability for cancer care quality assessment and public reporting, and should be considered. In phase 2, we will apply the measures at the physician group level, and assess the feasibility of public reporting at the physician group level.
Meloxicam, a selective cyclooxygenase-2 (COX-2) inhibitor, enhances the response to carboplatin and weekly paclitaxel in advanced non-small cell lung cancer (NSCLC)
Authors: O. Nishiyama, H. Taniguchi, Y. Kondoh, T. Kimura, K. Kato, Y. Tanikawa, M. Aoyama, R. Suzuki, K. Shimokata
Journal: Journal of Clinical Oncology (2005)

7312 Background: Constitutive overexpression of COX-2 is common in NSCLC, and this could be linked to tumor progression. Some preclinical studies suggest that a selective COX-2 inhibitor may augment the antitumor effects of chemotherapy. In this study, patients with advanced NSCLC were treated with meloxicam, a selective COX-2 inhibitor, in combination with carboplatin and paclitaxel, to test the hypothesis that meloxicam enhances the response to the chemotherapy. End points were response rates and toxicity. Methods: Patients with stage IIIB or IV NSCLC were eligible. ECOG PS had to be 0 to 2, and prior chemotherapy was not allowed. Patients received paclitaxel 70mg/m2 weekly for 3 of 4 weeks with carboplatin (AUC 6) on day 1, as well as daily meloxicam (10mg/day). Results: Twenty-seven patients were treated: gender M/F; 21/6, median age; 64 yr (range, 48–74), stage IIIB/IV; 11/16, PS 0/1/2; 15/6/6, histology AD/SQ; 23 / 4. A median of 2 cycles (range, 1–6) were administered. Complete response was observed in 1 patient (4%) and partial response in 11 (41%), yielding an overall clinical response rate of 44%. Thirteen patients (48%) had stable disease. Five patients (19%) had grade 3 and 1 (4%) had grade 4 neutropenia. Grade 3 thrombocytopenia was observed in 2 (7%). Grade 3 or more non-hematological toxicities observed included anorexia and vomiting in 2 (7%), alopecia in 1 (4%), and fever in 2 (7%). Grade 2 peripheral neuropathy was observed only in 2 (7%). Conclusions: Meloxicam in combination with carboplatin and weekly paclitaxel chemotherapy is an efficacious and feasible regimen in patients with advanced NSCLC. Moreover, this study suggests that the addition of a selective COX-2 inhibitor may enhance the response to this regimen. No significant financial relationships to disclose.
Imatinib mesylate as first-line therapy in patients with chronic myeloid leukemia in accelerated phase and blastic crisis: A retrospective analysis.
Authors: N. K. Thota, S. Gundeti, P. Coca, J. Srirambhatla, R. Parimkayala, V. g. Linga, S. Bheemnathi Hanuman, L. S. Maddali, R. Digumarti
Journal: Journal of Clinical Oncology (2011)

6569 Background: There is a paucity of data on the efficacy and safety of imatinib as first line therapy in patients with chronic myeloid leukemia (CML)–accelerated phase (AP) and blast crisis (BC). In this regard, we retrospectively analyzed the outcomes of such patients at our institute from 2002 to 2009. Methods: We analyzed CML-AP and BC treatment naïve patients who had received at least 3 months of imatinib mesylate (IM) 600mg/day. Results: A total of 63 patients, with AP 39 (61.9%) and BC 24 (38%) were analyzed. The median age of patients was 35 years (8 – 61) with a male to female ratio of 1.1:1 (33: 30). Hematologic and cytogenetic response are depicted in the table. Median time to attain CHR was 3 months (1-30). More than two-thirds of patients attained major cytogenic response at 12 months. Dose interruption was necessary in only 11% of patients due to bone marrow suppression. At a median follow up of 28 months (3–88), 34 (53.96%) patients remained in complete remission and had not progressed. Median progression free survival was 17.25 months (3–56) and 14 months (5–61.25) in AP and BC respectively. Median overall survival was not reached in AP and BC. Conclusions: Imatinib as monotherapy achieves good hematological and cytogenic responses in chemotherapy naive patients with CML AP and BC, with an acceptable level of toxicity. Complete hematologic response (CHR) ≤ 3 months 6 months AP (n=39) BC (n=24) Total (n=63) AP (n=31) BC (n=24) Total (n=63) No (%) 19 (48%) 12 (50%) 31 (49%) 27 (87%) 18 (75%) 45 (71%) Cytological response 6 months 12 months Response (% metaphases Ph +VE) AP (n=39) BC (n=24) Total (n=63) AP (n=28) BC (n=16) TOTAL (n=44) Complete (0) 11 (17%) 5 (7%) 16 (25%) 22 (34%) 13 (20%) 35 (55%) Partial (1–35) 3 (4%) 7 (11%) 10 (15%) 3 (4%) 2 (3%) 5 (7%) Minor (36–65) 15 (23%) 6 (9%) 21 (33%) 3 (4%) 1 (1.5%) 4 (5.5%) Minimal (66–95) 5 (7%) 2 (3%) 7 (11%) None (>95) 2 (3%) 2 (3%) 4 (6%) Not evaluated* 3 (4%) 2 (3%) 5 (7%) *death or lost to follow up
P0-Related Protein Accelerates the Migration of Human Mesenchymal Stem Cells and Their Progeny by Modulating VLA-5 Interactions with Fibronectin.
Authors: Suzanne M. Watt, Maria Roubelakis, Sinead Forde, Fengjuan Lu, Grigorios Tsaknakis, Enca Martin-Rendon
Journal: Blood (2006)