tbuckley/cabot-search huggingface dataset:
Overutilization of IMRT/IGRT in treatment of rectal cancer: Cost implications of deviation from evidence-based practices.
Authors: Heather A Curry, Arlene A. Forastiere, William A. Flood, Elaine Whyler, John Peter Plastaras, Neha Vapiwala
Journal: Journal of Clinical Oncology (2014)

34 Background: Current evidence-based guidelines for management of rectal cancer (RC) caution against routine use of IMRT and do not address the role of IGRT. To explore patterns of care and cost implications for treatment of RC in commercially insured patients, we assessed treatment requests submitted for preauthorization through eviti Connect. Methods: A proprietary web-based application enables oncology providers to obtain automated precertification for patients insured by payers across the US that use the platform. All requests for pelvic radiation for treatment of RC submitted from 6/1/11-5/31/14 were reviewed. Treatment delivery costs for 3D CRT + weekly port films and for IMRT + IGRT were calculated based on average reimbursement rates from 3 payers for a typical course of 50.4 Gy/28 fractions. Results: A total of 195 cases for treatment of RC were submitted. At submission, 50.3% (98/195) of cases met evidence based standards and received automated preauthorization; 49.7% required treatment justification. Ninety-eight percent of deviations involved use of IMRT and/or IGRT. Upon review, 34.9% (68/195) had a medical rationale for the variance. Justification for IMRT/IGRT use included treatment volumes comparable to anal cancer, inadequate bowel displacement by routine techniques, and obesity. Fifteen percent (29/195) contained unwarranted deviations. In 23/29 cases peer to peer discussion resulted in the provider altering the plan to be compliant. Providers did not agree to changes in the other 6 cases. Cost for a course of 3D CRT + weekly port films was $6,591 vs. $32,292 for IMRT + daily IGRT. For these 195 cases, the estimated cost of overutilization of IMRT/IGRT was $745,000 ($25,700 X 29). Conclusions: Despite lack of endorsement by consensus group guidelines, IMRT and IGRT were prescribed for treatment of RC in nearly 50% of cases. Case review and peer to peer discussion clarified the rationale for treatment deviations from guidelines and allowed providers to bring plans into compliance with evidence based practices, reducing inappropriate use of IMRT/IGRT from 15% to 3%. Reduction in unwarranted use of high cost technologies can improve quality and yield significant cost savings.
KCNMA1 cooperating with PTK2 is a novel tumor suppressor in gastric cancer and is associated with disease outcome
Authors: Gaoxiang Ma, Hanting Liu, Qiuhan Hua, Meilin Wang, Mulong Du, Yadi Lin, Yuqiu Ge, Weida Gong, Qinghong Zhao, Fulin Qiang, Guoquan Tao, Zhengdong Zhang, Haiyan Chu
Journal: Molecular Cancer (2017)

Inactivation of tumor suppressor genes by promoter hypermethylation plays a key role in the tumorgenesis. It is necessary to uncover the detailed pattern of whole genome-wide abnormal DNA methylation during the development of gastric cancer (GC). We performed a genome-wide methylation detection using 12 paired of GC tissues and their corresponding normal tissues. Methylation-specific PCR (MSP) and bisulphite sequencing (BSP) were used to measure methylation status of specific CpG site. Based on the bioinformatic analysis, the cell phenotypes and mouse model experiments were constructed to detect effect of the target gene. Using the Kaplan–Meier survival curve, the clinical value of KCNMA1 was assessed in GC patients. The CpG site cg24113782 located at the promoter of KCNMA1 showed the most significant difference, contributing to the commonly silenced KCNMA1in gastric cancer cells and primary GC tissues. The promoter methylation of KCNMA1 was detected in 68.7% (77/112) of tumor tissues, compared with 16.2% (18/112) of normal tissues (P < 0.001). The survival curve indicated that KCNMA1 hypermethylation was significantly associated with the shortened survival in GC patients (P = 0.036). KCNMA1 significantly inhibited biological malignant behavior of gastric cancer cell by inducing cell apoptosis in vitro, and suppressed xenograft tumor growth in subcutaneous mouse models (both P < 0.001). Furthermore, the anti-tumor effect of KCNMA1was mediated through suppressing the expression of PTK2. KCNMA1 is a critical tumor suppressor in gastric carcinogenesis and its hypermethylation is an independent prognostic factor in patients with gastric cancer.
EGFR expression in invasive anal carcinoma.
Authors: A. A. Paliga, R. Onerheim, A. Gologan, A. Spatz, T. Vuong
Journal: Journal of Clinical Oncology (2011)

412 Background: Squamous cell anal carcinoma (SCAC) treatment remains unchanged since the institution of chemoradiation over 4 decades ago. Epidermal growth factor receptor (EGFR) is a protein often expressed in aggressive cancers and that is the target of the monoclonal antibody: cetuximab. Concurrent cetuximab and radiation has been particularly effective treating squamous cell carcinoma of the head and neck. Like head and neck cancer, anal cancer is an epithelial tumor of the alimentary tract that is radioresponsive and is associated with HPV infection. The rarity of this cancer limits its evaluation for biological markers. This study set out to thoroughly characterize EGFR expression by immunohistochemistry in 101 invasive SCAC tissue samples. Methods: One hundred and one pretreatment paraffin embedded invasive SCAC biopsies, obtained from the Montreal area between 1999 and 2009, were tested for EGFR expression by immunohistochemistry. All samples were confirmed to harbor invasive anal carcinoma on H&amp;E slide preparations. Corresponding cancerous areas were identified on paraffin tissue blocks and cut out for tissue microarray analysis. Samples were immunostained with an EGFR antibody (clone SPM 341) on the Discovery XT Autostainer (Ventana), and staining was assessed by light microscopy by two pathologists. A semiquantitative combination score combining staining intensity with the percent of cells staining gave a final score: just detectable or weak (1+); moderate (2+); strong/intense (3+). Results: Of 101 patient biopsies, 82 samples had sufficient material for interpretation. Of these samples, 72/82 (90%) stained positive for EGFR, while 41/82 (50%) samples displayed at least moderate to strong staining. Conclusions: This is the largest cohort of SCAC tissue samples tested to date for EGFR expression and it confirms that the vast majority of invasive SCAC overexpress EGFR. EGFR likely plays a role in anal cancer tumor-genesis and progression. Testing of EGFR inhibitors in this patient population is justified. No significant financial relationships to disclose.
Exercise and side effects among 417 older patients with cancer during and after cancer treatment: A URCC CCOP study.
Authors: L. Sprod, S. G. Mohile, K. Devine, M. C. Janelsins, L. J. Peppone, G. R. Morrow, R. S. Lord, H. M. Gross, K. M. Mustian
Journal: Journal of Clinical Oncology (2011)

9036 Background: The number of older (>65 yrs) and oldest old (>80 yrs) cancer patients (pts) is increasing. Older pts may have more side effects and functional deficits from treatments. Exercise (EX) is a promising intervention for improving side effects and function but little is known about these relationships among older cancer pts. We report on EX participation during and after treatment (tx) and identify associations between EX and side effects and self-rated health (SRH) in older cancer pts. Methods: 417 newly diagnosed older cancer pts (mean age=73, range=65-92; N=47 >80 yrs) receiving chemotherapy and/or radiation were recruited from 20 CCOP sites in the U.S. Pts reported on EX participation (yes/no), side effects [pain, fatigue, nausea, sleep problems, depression, shortness of breath (SOB), memory problems, weight loss, hair loss, concentration difficulties, hot flashes, and skin problems; 0-10 rating scale; 10=worst], and SRH (1-5 rating scale; 1=excellent) during and in the 6-months (mo) after tx. Results: 46% of older and 41% of oldest old pts reported using EX during tx. 60% of older and 68% of oldest old pts reported using EX after tx. ANOVAs revealed that older pts who used EX compared to no EX during tx reported significantly less weight loss (EX=1.43, no EX=2.01), SOB (EX=1.96, no EX=2.84), and better SRH (EX=2.37, no EX=2.88) during tx. Older pts who used EX during tx reported less SOB (EX=1.34, no EX=2.14) and better SHR (EX=2.44, no EX=2.85) after tx. The oldest old pts who used EX during tx compared to no EX reported less concentration difficulties (EX=1.20, no EX=3.05) and memory problems (EX=1.67, no EX=4.14) during tx. The oldest old who used EX compared to no EX in the 6 mo after tx reported less nausea (EX=0.19, no EX=1.60), fatigue (EX=3.14, no EX=5.90), and total side effects (EX=15.14, no EX=30.10) after tx. All p<0.05. There was a trend (all p<0.10) toward reduced sleep problems (EX=2.00, no EX=4.20) and skin problems (EX=0.67, no EX=2.90) in pts who used EX compared to no EX in the 6 mo after tx. Conclusions: Almost half of older and oldest old cancer pts report using exercise during and after treatments. Older pts are amenable to exercise during and following treatments and exercise may reduce side effects.
Initial change in tumor size as an imaging surrogate of outcomes in patients with metastatic colorectal cancer (mCRC) treated with first-line irinotecan and 5-FU combination chemotherapy.
Authors: C. Suzuki, L. Blomqvist, A. Sundin, P. Bystrom, A. Berglund, H. Jacobsson, P. Nygren, B. Glimelius
Journal: Journal of Clinical Oncology (2011)

3569 Background: Changes in tumor size using WHO RECIST-criteria have been extensively employed to monitor palliative chemotherapy and describe objective treatment response (OR). Few have questioned the fixed thresholds for response evaluation, particularly using RECIST and the relevance of an OR for patient prognosis is unclear. The aim was to determine whether the magnitude of change in tumor size at the first follow-up CT-examination after baseline examination (first change) correlates with outcome in patients with metastatic colorectal cancer (mCRC) treated with combination chemotherapy. Methods: The first change was retrospectively analyzed in a multicenter randomized phase III trial (Nordic VI, n=567) comparing first-line irinotecan with either bolus or infused 5-FU. Cox proportional hazards multiple regression model and Kaplan-Meier survival analyses after correction for guarantee-time bias were performed to evaluate correlations between first change, OR according to RECIST 1.0, progression-free survival (PFS) and overall survival (OS). Results: The first change strongly correlated with best OR (p<0.0001). The hazard ratio (HR) for PFS and OS decreased continuously along with first change. A decrease of 50% or more indicated a very favorable prognosis relative to an increase<10% [HR = 0.25 (95%CL 0.13-0.49) for OS and 0.35 (95%CL 0.21-0.59) for PFS]. Patients with the appearance of new lesions or unequivocal progression of non-measurable lesions had a worse prognosis than those with only an increase in size of more than 20%. Conclusions: The change in tumor size at the first follow-up CT is a potent imaging surrogate of chemotherapy-induced tumor response and is strongly prognostic for PFS and OS in mCRC. The comparison of cytotoxic treatments in a trial can thus potentially be achieved more rapidly by the first change approach than to wait for maximal response evaluation using RECIST.
Safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity of the oral AKT inhibitor GSK2141795 (GSK795) in a phase I first-in-human study.
Authors: H. A. Burris, L. L. Siu, J. R. Infante, J. J. Wheler, C. Kurkjian, J. Opalinska, D. A. Smith, J. M. Antal, J. L. Gauvin, T. Gonzalez, L. M. Adams, P. Bedard, J. F. Gerecitano, R. Kurzrock, K. N. Moore, S. R. Morris, C. Aghajanian
Journal: Journal of Clinical Oncology (2011)

3003 Background: GSK795 is a potent pan-isoform inhibitor of AKT. The objectives were to define the maximum tolerated dose (MTD), and to evaluate the PK, PD and clinical activity of GSK795 in patients (pts) with advanced solid tumors. Methods: GSK795 was given orally, once daily (QD) in this two-part study of dose-escalation (Part 1) with expansion (Part 2) at the MTD in selected tumor types to evaluate the clinical activity. Alternative dosing schedules were also investigated. Results: Preliminary data are available for 66 pts that received ≥ 1 dose of GSK795, including pts with endometrial (12) and prostate cancer (9) as well as other tumor types selected for either PTEN loss or PIK3CA mutation (7). Doses explored were 10, 20, 40, 75, 100 and 150mg QD. The MTD was 75 mg QD. Dose-limiting toxicities were G3 hyperglycemia (n=2), G4 hypoglycemia (n=1), G3 hypoglycemia (n=1), and G2 stomatitis (n=1); all were reversible. The most common (>10%) drug-related adverse events were diarrhea (47%; G3/4 0%), nausea (33%; G3/4 0%), fatigue (26%; G3/4 0%), vomiting (18%; G3/4 0%), decreased appetite (15%; G3/4 0%), dyspepsia (15%; G3/4 0%), hyperglycemia (15%; G3/4 11%), and rash (15%; G3/4 3%). AUC (0-24) and Cmax generally increased in a dose-proportional manner. Median Tmax was 2 to 3 hr and the effective t½ ranged from 2.0 to 5.5 days. 6/7 pts dosed at ≥75mg QD given a carbohydrate challenge at baseline and steady state exhibited either increased post-prandial glucose values, or a delay in the return to baseline of post-prandial values, suggesting a PD effect of GSK795 on glucose. One pt with anal cancer (PIK3CA and PTEN status unknown) had a partial response. 5/ 12 evaluable endometrial pts are still on trial; 2 of these pts with PIK3CA mutation and/or PTEN loss have had stable disease (↓25% and 0%) for ≥ 6 months. 6/ 9 evaluable prostate pts are still on trial; 2 of these pts with partial or complete PTEN loss have had SD (bone only disease) ≥ 6 months. Conclusions: The AKT inhibitor GSK795 has been well tolerated with reversible, predictable toxicities and PD evidence of target inhibition. Tumor decreases and SD ≥ 6 months has been observed in pts with an activated PI3K/AKT pathway.
The Virginia Mason Pancreatic Cancer Database.
Authors: V. J. Picozzi, M. Nguyen, L. W. Traverso, R. A. Kozarek
Journal: Journal of Clinical Oncology (2011)

191 Background: Pancreatic cancer (PC) is associated with poor overall survival (OS);1-year PC OS PC is only 24% (ACS Facts and Figures 2010). We created a database (DB) intended to analyze clinical outcomes for the composite PC population treated at our institution. Methods: Inclusion of patients (pts) in the DB required: 1) identification by ICD code 157.9, and 2) all active therapy elements (surgery, radiotherapy, and/or at least 1 cycle chemotherapy) executed at our institution. Among DB datafields are pt age, sex, and performance status, tumor stage, tumor size, node and margin status (resected pts), staging laparoscopy results (if performed), liver involvement (metastatic pts), anticancer therapies administered, time and site of disease progression (if applicable), cause of death and clinical trial participation. Data is updated quarterly; patients are censored for OS if care is transferred or death occurs.The DB can interface with other clinical/administrative databases within our system. Results: From 1/1/2008 to 6/30/2010, 491 pts with ICD code 157.9 were identified. 307/491 (63%) pts did not meet DB inclusion criteria. Reasons included consultation only (n=211), palliative care only (n=52), therapy shared with other institutions (n=42), unknown (n=2). Of the remaining 184 pts, 38 pts (21%) were resected, 27pts (15%) were borderline resectable per institutional criteria, 44 pts (24%) were locally advanced/nonresectable and 75 pts (40%) had metastatic disease. 65% of pts wre &gt;60 years old (median age 65 yrs) 30/184 pts (16%) were ECOG PS 2 or higher. 5/184 (3%) transferred care or were lost to c; thus 179 pts were fully evaluable for OS. Current median follow-up of all pts is 13.6 mo. 101/179 (61%) pts are presently alive; 1-yr OS of the entire patient population is 69% (Kaplan-Meier). 1-yr OS by disease category includes 94% resected, 81% borderline resectable, 78% locally advanced/nonresectable, and 44% metastatic disease. The DB will be continuously updated and developed. Conclusions: 1) The general characteristics of pts in our DB are comparable to literature expectations. 2) The DB provides guidance as to the effectiveness of institutional therapy for our entire PC population. 3) A variety of potential DB applications exist. We anticipate continued DB development. No significant financial relationships to disclose.
Long-Term Outcome of ATL Patients Who Underwent Reduced-Intensity Stem Cell Transplantation (RIST): Suggested Potent Graft-Versus-ATL and HTLV-1 Effects.
Authors: Ryuji Tanosaki, Kimikazu Yakushijin, Yoshitaka Asakura, Saiko Kurosawa, Nobuhiro Hiramoto, Masakazu Mori, Takahiro Fukuda, Sung-Won Kim, Shin-ichiro Mori, Yuji Heike, Kensei Tobinai, Yoichi Takaue
Journal: Blood (2009)
Phase II trial of becatecarin (rebeccamycin analogue) in relapsed sensitive small cell lung cancer (SCLC)
Authors: A. Dowlati, T. Mekhail, T. O’Brien, K. Rutherford, M. Snell, A. Ness, P. Ma, S. P. Ivy, B. Halmos
Journal: Journal of Clinical Oncology (2008)

19060 Background: Relapsed SCLC carries a poor prognosis. Toposiomerase I and II inhibitors are considered amongst the most active agents against SCLC. Becatecarin (rebeccamaycin analogue-RA) is an anti-tumor antibiotic with inhibitory activity against both topoisomerase II and I as well as DNA intercalating properties. We performed a phase II trial of RA in relapsed sensitive SCLC with the primary endpoint of determining the response rate, survival and toxicities related to this agent. Methods: A Simon 2-stage design was employed were initially 20 patients would be treated; if > 1 response was observed a total of 35 would be enrolled. Patients received RA at a dose of 140 mg/m2/d i.v. over 1 hour on daily × 5 schedule repeated every 21 days for a maximum of 6 cycles. Response was evaluated every 2 cycles. Eligibility included relapsed SCLC (i.e. recurrence > 60 days from completion of first line chemotherapy), ECOG PS 0,1,2 and adequate organ function. Results: The first stage of enrollment has been completed with 20 evaluable patients (M/F:10/10). A total of 49 cycles have been administered to date (median 2.4 range 1–6). Two partial responses have been observed. Four patients had stable disease. No treatment-related deaths have been reported. Grade 4 neutropenia and thrombocytopenia occurred in 10% and 4% of cycles respectively. Two cases of febrile neutropenia occurred. Other grade 3 toxicities coded as possibly or definitely related to treatment include 1 instance of grade 3 nausea and vomiting and one case of ataxia. Conclusions: Early evidence suggests that RA has activity in relapsed SCLC and toxicities are manageable. (Supported by Grants U01 CA62502 and K23 CA109348–01) No significant financial relationships to disclose.
A phase I/II study of cisplatin and radiation in combination with sorafenib in cervical cancer: Evaluation of biomarkers.
Authors: C. A. Townsley, M. Milosevic, M. A. Haider, H. Mackay, I. Yeung, S. Kim, W. Levin, L. Manchul, S. Bindra, K. MacAlpine, L. M. Tinker, L. Wang, J. Quintos, A. W. Fyles, A. M. Oza
Journal: Journal of Clinical Oncology (2011)

5037 Background: This is a single-arm, open-label, phase I/II trial in patients with early stage carcinoma of the cervix investigating the addition of sorafenib (S), a dual kinase inhibitor with anti-VEGF properties which may increase the affect of chemotherapy and radiation on tumor cells. Methods: All patients received conventional treatment with radiation and chemotherapy (RTCT) but a low risk/para-aortic group received S alone in escalating doses for 1 week prior to the start of (RTCT), while high risk patients received S alone in escalating doses for 1 week prior to the start of RTCT, plus concurrently with RTCT. Biomarkers of response to S were measured at baseline, after 7 days of S alone (400 or 800 mg daily) and after 1 week of RTCT. Three Magnetic Resonance (MR) biomarkers of perfusion and vascular permeability were evaluated: 1. Enhancement fraction at 25s (EF25) - indicative of early phase enhancement; 2. Relative signal intensity (RSI) - indicative of late phase enhancement; and 3. iAUC60. In addition, tumor median pO2 (mpO2), hypoxic proportion (HP) and interstitial fluid pressure (IFP) were measured using needle-based techniques. The paired Wilcoxin signed ranks test was used to evaluate differences in the biomarkers relative to baseline. Results: Thirteen patients have been enrolled onto the study and the low risk cohort is complete. Most common toxicities of any grade include diarrhea (82%), lymphopenia (82%), and nausea (82%). Tumor volume increased with 7 days of S alone (86 vs 78 cm3, p<0.01), and EF (73 vs 86%, p=0.02) were decreased and RSI (1.7 vs 1.9, p=0.07) was unchanged. The tumors also became more hypoxic (mpO2 3 vs 14 mm Hg, p=0.01; and HP 67 vs 51%, p=0.06) but there was no change in IFP (21 vs 24 mm Hg). MR biomarkers were also obtained in week 2 (after the start of RTCT) for 12/13 patients, IFP in 10 and mpO2/HP in 7. Tumor volume decreased (57 vs 81 cm3, p=0.01) and there was a significant reduction in IFP (16 vs 24 mm Hg, p=0.04). However, EF, RSI, mpO2 and HP were not significantly different from baseline. Conclusions: Thus study demonstrates that the combination of RTCT and S is tolerable and that biomarkers show increasing hypoxia, and indications of reductions in markers of vasculature with S.
Impact of the chronic kidney disease epidemiology collaboration (CKD-EPI) equation for estimating renal function on eligibility for cisplatin-based chemotherapy in patients with bladder cancer.
Authors: C. Tsao, S. M. Seng, S. Grossman, W. K. Oh, M. D. Galsky
Journal: Journal of Clinical Oncology (2011)

e15139 Background: Cisplatin-based chemotherapy is standard treatment for patients with advanced bladder cancer. However, a large proportion of patients with advanced bladder cancer are ineligible for cisplatin-based chemotherapy due to impaired renal function. Though the Cockroft-Gault (CG) equation is generally utilized to estimate renal function and determine “cisplatin eligibility,” the CKD-EPI equation (Levey, Ann Intern Med, 2009) has recently emerged as the preferred method for calculating glomerular filtration rate (GFR). We sought to determine the impact of methods of estimating renal function on “cisplatin eligibility.” Methods: The Mount Sinai Data Warehouse was utilized to identify all patients diagnosed with bladder cancer at our institution between 1/1/2000 and 1/1/2011. Variables extracted for analysis included gender, race, age, weight, and serum creatinine. Patients with missing data, age <18 or >110, or a creatinine of < 0.6 or > 7 mg/dl were excluded. For each patient, CrCl was estimated using the GC equation and GFR was estimated using the Modification of Diet in Renal Disease (MDRD) and CKD-EPI equations. Patients were considered cisplatin-ineligible if CrCl or GFR was < 60. Results: 567 patients with bladder cancer were identified; 54 were excluded for creatinine range, 82 for duplicate entries, 82 for missing data, and 1 for age limit. 409 patients, with a median age of 78 (range, 37-103) were included in the final analysis. The results are detailed in the table. Conclusions: The CG formula substantially overestimates the proportion of cisplatin-ineligible patients based on a standard renal function threshold. Use of the more precise CKD-EPI equation should be considered when evaluating suitability for cisplatin in patients with bladder cancer. Formula Median CrCl or GFR (range) Cisplatin-ineligible CG 54 (4-215) 232/409 (57%) MDRD 64 (6-154) 180/409 (44%) CKD-EPI 64 (6-128) 179/409 (44%)