tbuckley/cabot-search huggingface dataset:
A randomized, double-blind placebo-controlled phase II study of FOLFOX with or without GDC-0449 (vismodegib) in patients with advanced gastric and gastroesophageal junction carcinoma (NCI 8376).
Authors: D. J. Cohen, L. Liebes, R. Xu, N. Takebe, J. A. Sparano
Journal: Journal of Clinical Oncology (2011)

TPS173 Background: The hedgehog (Hh) pathway is an evolutionally highly conserved signaling cascade important for control of many developmental processes. It is critical in gastroesophageal (GE) embryogenesis and normal cell growth and survival. The Hh pathway is also implicated in GE cancer formation and progression.(Berman, 2003; Rubin, 2006; Ma, 2005; Ohta, 2005) Pathway overexpression has been demonstrated preclinically in GE tumors and the degree of activation correlates with clinical and histologic features. Hh antagonists have demonstrated a dose dependent reduction in GE tumor growth as well as inhibition of cell motility and invasiveness. (Yanai, 2007; Yoo, 2008) GDC-0449 is an oral small-molecule antagonist of the Hh pathway which binds to and inhibits SMO thereby blocking Hh signal transduction. This study will provide data on efficacy and safety of GDC-0449 plus FOLFOX relative to a current standard of care (FOLFOX alone) as 1st line treatment in pts with advanced GE cancers. Methods: This is an NCI-sponsored multicenter randomized, placebo controlled phase II study of FOLFOX with and w/o GDC-0449 in pts with advanced treatment-naive GE adenocarcinoma. Pts are randomized 1:1, stratified by institution and disease status (with or w/o distant mets) to treatment with FOLFOX(ox 85 mg/m2 IV d1, leucovorin 200 mg/m2 IV d1, 5-FU 400 mg/m2 IV bolus d1, 5-FU 2400 mg/ m2 CI over 48 hrs) q14d with GDC-0449/placebo 150mg PO qd continuously. FFPET and blood samples will be collected for biomarker analyses. Primary endpoint is PFS and 116 pts are required to achieve 90% power to detect a 69% increase in median PFS (9.8 vs. 5.8 mo), at the 1- sided 0.10 significance level. Secondary objectives are OS, RR, and toxicity rates. Exploratory objectives include investigation of correlations b/t baseline tumor Hh pathway expression and tumor genetic variation with efficacy, measurement of serum growth factor levels and shed collagen epitopes as a surrogate for response in the microenvironment, and correlation of circulating endothelial progenitor cells with response. 58 patients are currently enrolled and accrual continues. Supported by: N01-CM-62204.
Non-thoracic MRI does not cause problems with pacemakers or implantable defibrillators, study finds
Authors: Susan Mayor
Journal: BMJ (2017)

Magnetic resonance imaging (MRI) scans of areas other than the chest are not associated with problems with pacemakers or implantable cardiac defibrillators (ICDs) in patients with these devices, a large registry study has found.1

Having a cardiovascular implantable electronic device has been a contraindication for MRI because of concerns that exposure to the magnetic field could cause the device’s leads to heat up, resulting in myocardial thermal injury and changes in pacing properties. Cardiac devices are now designed to reduce these risks, but many …
A risk-adapted strategy of radiotherapy and cisplatin-based chemotherapy in stage II seminoma: Results of a 20-year experience
Authors: J. Domont, A. Laplanche, R. de Crevoisier, C. Theodore, P. Wibault, K. Fizazi
Journal: Journal of Clinical Oncology (2005)

4571 Background: Indications for radiotherapy (RT) and chemotherapy (CT) in stage II seminoma are debated. From 1982 to 2001, the policy at Institut Gustave Roussy was to treat patients (pts) with stage IIA-IIB disease with external RT (35 Gy) targeting the retroperitoneal lymph nodes (+ the mediastinum and supra-clavicular area until 1992) and pts with IIB-IIC disease with cisplatin-based CT. In stage IIB, 3 cm was the typical larger tumor size selected for RT. Methods: We retrospectively reviewed 59 consecutive pts with stage II seminoma who were treated in our institution according to this policy. Results: Median age was 40 years (range: 23–61). Pts had stage IIA (n= 9), stage IIB (n=26), and stage IIC (n=24) disease. Among the 30 pts who received RT, 8, 20, and 2 had stage IIA, IIB, and IIC disease, respectively. Among the 29 patients who received CT, 0, 7, and 22 had stage IIA, IIB, and IIC disease, respectively. They received EP (n=20), BEP (n=3), HOP (n=3), PVB (n=2), and VAB-6 (n=1). With a median follow-up of 7 years (range 0–21), 18 relapses occurred (31%), including 9 cases treated with RT (30%) and 9 others with CT (31%). The 5-year relapse-free survival was 69% (CI 95%: 56–79). All relapses but one was salvaged with CT ± followed by surgical resection of residual masses and only 1 pt died of seminoma. The 5-year overall survival is 98% (CI 95%: 91–100). Four patients developed a second cancer: 3 had received RT and their second cancer occurred in the radiation field (colo-rectal carcinoma, oesophageal cancer, and medullary thyroid carcinoma) and 1 pt had received CT (colo-rectal carcinoma). Conclusions: The overall outcome of patients with stage II seminoma treated according to this risk-adapted strategy is excellent. To reduce the risk of relapse, 1) indications for CT could be extended to all stage IIB lesions and 2) post-CT residual masses could be evaluated with PET scan to identify pts likely to have active disease and therefore to select them for additional treatment. No significant financial relationships to disclose.
Association of colorectal cancer intrinsic subtypes with prognosis, chemotherapy response, deficient mismatch repair, and epithelial to mesenchymal transition (EMT).
Authors: Ramon Salazar, Paul Roepman, Josep Tabernero, Andreas Schlicker, Ian Majewski, Victor Moreno, Robert Rosenberg, Scott Kopetz, Lodewyk F. A. Wessels, Rene Bernards, Iris Simon
Journal: Journal of Clinical Oncology (2013)

3530 Background: Unbiased genome-wide analyses of gene expression patterns have been successfully used for molecular classification of breast cancer into subtypes that have clear relevance for prognosis and treatment. A similar classification is still missing for colorectal cancer (CRC). Methods: Using full genome expression data of 188 stage I-IV CRC patients, an unsupervised clustering revealed three major subtypes (A-, B-, C-type). A molecular subtype classification was developed and validated in 543 stage II and III patients. The subtypes were analyzed for correlation to clinical information, mutations in the kinome, known molecular markers status and chemotherapy response. In addition, subtypes were determined on 173 samples from The Cancer Genome Atlas (TCGA) colon dataset with Agilent genome expression data. Results: C-type patients have the worst outcome, a mesenchymal phenotype, and show no benefit from adjuvant chemotherapy treatment. Patients having A- or B-type tumors have a better clinical outcome, a more proliferative and epithelial phenotype and benefit from adjuvant chemotherapy. A- and C-type groups are enriched for tumors having oncogenic BRAF mutations and a deficient DNA mismatch repair system. B-type tumors showed a low overall kinome mutation frequency (1.6%), while both A- and C-type patients harbor a higher mutation frequency (respectively 4.2 and 6.2%), in agreement with their mismatch repair deficiency. Finally, CRC subtyping was confirmed in the colon TCGA dataset with 26 samples classified as A-type, 110 as B-type and 37 as C-type. In agreement with the different aggressiveness of the subtypes, A-type tumors were less prevalent in stage IV while C-type were less prevalent in stage I CRC. Conclusions: The heterogeneity of the intrinsic subtypes is largely based on three biological hallmarks of the tumor: an epithelial-to-mesenchymal transition, deficiency in mismatch repair genes that result in a high mutation frequency associated with MSI, and cellular proliferation. These subtypes are clinically relevant, as they differ in their underlying biology and might require different treatment strategies.
PD-1 expression on classical monocytes (CM) as an independent predictor of cancer specific survival in clear cell renal carcinoma (ccRCC).
Authors: Mohammed Haseebuddin, Alexander Macfarlane, Karen Ruth, Robert G. Uzzo, Elizabeth R. Plimack, Mowafaq Jillab, Essel Dulaimi, Tahseen I. Al-Saleem, Kerry Campbell
Journal: Journal of Clinical Oncology (2016)

562 Background: We have previously shown that PD-1 expression in peripheral blood lymphocytes is elevated in RCC patients at diagnosis and decreases subsequent to surgery. We theorize that classical monocyte (CM) inhibition through PD-1 interferes with antigen presentation necessary to stimulate adaptive immune responses, and, thus, preop CM PD-1 expression is prognostic of poor outcomes. Methods: Blood samples were obtained from RCC patients (n = 90) preop and age-matched healthy donors (n = 25). Flow cytometric (FC) data were quantified as mean fluorescence intensity (MFI) or % of cells that express a biomarker. Patients were excluded if they had comorbid CLL, had prior surgeries for RCC, had non-ccRCC histology, or if the FC data was missing. We have defined elevated CM PD-1 expression at the third quartile level of CM PD-1 expression (784 MFI) in the healthy donors. CM PD-1 level was correlated with patient clinico-pathologic data using non-parametric tests. Cancer specific survival (CSS) curves were estimated with Kaplan-Meier methods and a multivariate analysis was performed. Results: The average age of the ccRCC cohort (n = 68) was 60 (range 25-88) years. 35 patients were Fuhrman Grade III/IV high-grade (HG) histology. With median follow-up of 41 months, 10 patients died with ccRCC. No patients with low-grade disease died. Median CM (%) was lower in those who died of disease compare to censored (64% vs 52%, p = 0.029). Patients with CM PD-1 expression &gt; 784 MFI had lower survival compared to patients with CM PD-1 &lt; 784 MFI (p = 0.02). Among HG patients, CSS at 24 months for CM PD-1 MFI &gt; 784 was 62.1% (95% CI 34.2-81.0) vs 93.3% (95% CI 61.3-99.0) for CM PD-1 MFI &lt; 784. On multivariable analysis, controlling for stage related covariates, CM PD-1 MFI &gt; 784 is associated with inferior CSS (hazard ratio = 5.1 [95% CI: 1.1-24.4], p = 0.04) among HG disease patients. Conclusions: In patients with ccRCC, an elevated preoperative CM PD-1 MFI level was associated with lower survival independent of pathological T stage and localized disease status. Preoperative CM PD-1 MFI may be an important biomarker to stratify patients at risk for poor outcome who may benefit from immunotherapy.
Quality Oncology Practice Initiative (QOPI) certification applicants and outcomes.
Authors: T. Gilmore, M. N. Neuss, P. Kadlubek, J. O. Jacobson
Journal: Journal of Clinical Oncology (2011)

e16599 Background: In addition to achievement of a minimum threshold on a series of performance indicators, ASCO QOPI Certification requires that practices demonstrate adherence to 17 chemotherapy standards involving staff education, chemotherapy planning, preparation and administration, and patient assessment, consent and education. Methods: In the first year, 69 practices applied for Certification and submitted their policies, procedures, and de-identified charts for review at QOPI offices. 25 also received an on-site review during which nurses observe practice and review charts. Results: Applicants were practices with<3 (47%), 4-7 (47%), 8-15 (21%) and >16 (11%) oncologists. 15% of practices met all 17 chemotherapy standards upon central review; 33% had one and 20% had two unmet standards; the largest number unmet was seven (two practices). The standard unmet most frequently (77%) related to qualifications of staff. 1/3 did not meet the standards for intrathecal chemotherapy or double-checking prepared dose. 18/25 practices met a greater number of standards when reviewed centrally vs. observed at audit; one vs. eight unmet standards for one practice. 1/3 had policies for recording current medications and 25% claimed adequate pathology/staging documentation but did not achieve compliance at audit. Practices with deficiencies were allowed to revise policies, educate staff, and submit documentation to demonstrate compliance. Of the 69 applicants, 55 are certified and 14 are working toward Certification. Conclusions: All practices must attest to the 17 safety standards the during application process; however QOPI review identified deficiencies for the majority of applicants. Nearly all of these practices were eventually able to achieve QOPI Certification. Participation in the QOPI certification process provides practices with a systematic way to examine and improve practice procedures and identify areas to enhance the safe administration of chemotherapy.
Physician data review to reduce cost per case and ALOS.
Authors: Susan Schreiner, Theresa Franco
Journal: Journal of Clinical Oncology (2013)

268 Background: Reducing costs in health care is critical due to declining reimbursement. Physicians are often unaware of how their practices affect the cost of patient care and may have difficulty in making changes. The leadership of the Cancer Service Line believed a more targeted approach in sharing data would improve physician understanding and engagement to assist in greater standardization and cost reduction. Methods: An education and communication strategy was developed that involves the leadership of each specialty section of oncology. A dashboard was created with metrics such as clinic visits, surgical volume, cost per case, average length of stay, and net income. The data is presented in monthly, quarterly and annual time frames with trends to highlight progress and identify areas for improvement. Monthly meetings are conducted with key stakeholders to obtain critical feedback. Results: Consistent data has increased physician understanding of clinical businesses the business is doing and has prompted them to optimize clinical schedules and improve operational efficiencies. Outpatient and inpatient data regarding cost per case, ancillary costs, pharmaceutical usage, blood product utilization, and drug exchanges has driven practice changes. The ALOS is at almost an entire day below benchmarks and direct cost per case is at budgeted target. Standardization has occurred in the use of blood products and there has been an intentional shift of some interventions to the outpatient arena. Conclusions: The implementation of a robust education and communication strategy have resulted in active engagement and participation of physicians, significant practice changes in cancer care and heightened understanding of the relationship of practice to cost. A dashboard that trends relevant metrics shared at regular intervals with key providers impact the cost of cancer services without affecting the quality.
Radiofrequency ablation for unresectable colorectal hepatic metastases: Prognostic factors and the effect of postoperative chemotherapy on survival.
Authors: Louis Ross, Eren Berber, Jamie Mitchell, Allan Siperstein
Journal: Journal of Clinical Oncology (2012)

581 Background: Radiofrequency ablation (RFA) is a recognized treatment modality in the management of patients with colorectal cancer liver metastasis (CRCLM). Our goal was to assess factors affecting long-term survival of patients undergoing RFA of CRCLM. Methods: We prospectively evaluated patients with unresectable CRCLM that underwent laparoscopic RFA. Patients were assessed pre- and postoperatively using triphasic computed tomography (CT) and intraoperatively using laparoscopic ultrasound. All information was entered into an IRB approved database. Pre-operative predictors were identified using Cox modeling. Postoperative chemotherapy was analyzed for its affect on survival. Results: 312 patients underwent 397 RFA sessions from 1999 to 2010. Patients averaged 2.7 lesions, with a dominant diameter of 3.4 cm and a preoperative CEA of 76. 28% had preoperative extrahepatic disease. Median survival on Kaplan-Meier analysis was 32 months, with 3 and 5 years survivals of 44% and 22%, respectively. The following were statistically significant on univariate and multivariable analysis: number of tumors (hazard ratio (HR) of 1.13 per tumor p=0.0002), dominate tumor diameter (HR 1.14 per cm p=0.03), pre-operative CEA (HR of 1.002 per one point rise p&lt;.0001), and pre-operative extrahepatic disease (HR 1.4 p=0.05). Post-operative chemotherapy was shown to improve survival after controlling for the presence of new disease in follow-up. Conclusions: To our knowledge, this is both the largest and longest follow-up of RFA for unresectable CRCLM. The number and size of tumors, and preoperative CEA value are strong predictors of survival whereas pre-operative extrahepatic disease had mild impact on survival. Post-operative chemotherapy was shown to improve survival after controlling for other factors.
Cytochrome P450 2D6 polymorphisms of Thai patients with breast cancer and their outcomes of adjuvant tamoxifen.
Authors: K. Pechatanan, S. Jaruhathai, T. Ativitavas, T. Sirisinha, R. Panvichian, V. Ratanatharathorn, E. Sirachainan
Journal: Journal of Clinical Oncology (2011)

e11037 Background: The clinical outcomes of breast cancer patients treated with tamoxifen may be influenced by the activity of cytochrome P450 2D6 (CYP2D6) enzyme because tamoxifen is metabolized by CYP2D6 to its active forms of antiestrogenic metabolite, 4-hydroxytamoxifen and endoxifen. We evaluated Cytochrome P450 2D6 SNPs and the influences of tamoxifen efficacy in adjuvant treatment of breast cancer in Ramathibodi hospital. Methods: Peripheral blood DNA samples from 38 patients who had disease recurrence during adjuvant tamoxifen treatment, and from 38 patients who had completed 5 years of tamoxifen without recurrence of breast cancer were isolated and genotyped for CYP2D6*4 by RFLP method, and CYP2D6*10 by PCR and DNA sequencing method. Disease free survival and correlation with genotypes were analyzed by Kaplan-Meier method, and log-rank test. Results: Of 76 analyzed patients, 42%, 36% and 22% of the patients carried the CYP2D6 *10/*10, wt/*10 and wt/wt genotypes respectively. There was no discernible correlation between clinicopathological parameters and the patterns of CYP2D6 *10 genotype. We found no significant difference in DFS among these three groups of patients (the mean DFS were 42.94 months for *10/*10 patients, not reach for wt/*10 patients and 60 months for wt/wt patients, p=0.128). One patient had both CYP2D6 wt/*4 and *10/*10. We found common SNPs of CYP2D6*10 188C>T with allele frequency 59.87 %. SNP of CYP2D6*4 1934G>T was detected with allele frequency 0.66%. Both SNPs frequencies were concordance to previous reports in Asian population. Conclusions: The polymorphisms of CYP2D6*10 do not influence the clinical outcomes of Thai breast cancer patients receiving adjuvant tamoxifen.
Effect of intervention on a quality measure of pain management at Medstar Washington Cancer Institute (MWCI).
Authors: Sekwon Jang, Vishal Navnitray Ranpura, Lynne Wood, Heller Stephanie, Linda Self
Journal: Journal of Clinical Oncology (2013)

e20700 Background: MWCI has participated in Quality Oncology Practice Initiative (QOPI) since 2008. Adherence to pain assessment and intensity documentation was high, but lower in plan of care for moderate/severe pain documentation (69%, compared to QOPI aggregate of 79%) during the Fall 2011 round. One potential explanation for the discrepancy was lack of communication between the nursing staff assessing the pain and the physician treating pain. We hypothesized that the use of pain card can improve the communication between nurses and doctors, as well as prompt physicians to document the plan of care for moderate/severe pain. Methods: MWCI created a team of physicians, nurses, quality resources and administrative staff in December 2011. We abstracted up to 10 patients charts per oncologist for those patientswho reported moderate to severe pain (pain score of more than 3 of 10 on numeric rating scale) each quarter during 2012.We used data for quarter 1 and 2 as a baseline. We implemented the use of pain card by nurses to report pain for these patients to the physician in quarter 3 and 4. Chi square test was used to compare documentation rate in the first two quarters and last two quarters. Results: The total number of charts evaluated, pain documentation as well as confidence intervals for each quarter are shown in the Table. Our results show significant improvement in pain documentation by physician in last two quarters compared to first two quarters (p =0.0007). Conclusions: Our study demonstrates pain card improved communication between nurse and physician resulting improved documentation of pain by physician. [Table: see text]
Risk of secondary urinary bladder cancer (UBC) in patients receiving radiotherapy for rectal cancer, prostate cancer, and gynecologic malignancies.
Authors: Paulo Gustavo Bergerot, Rebecca A. Nelson, Da-Wei Ye, Petros Grivas, Parminder Singh, Neeraj Agarwal, Toni K. Choueiri, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2016)

363 Background: Radiotherapy proximal to the bladder mucosa may incite malignant transformation. We investigated this phenomenon using a large population-based national database. Methods: The SEER13 database from 1992 to 2012 was reviewed for bladder cancer patients who had a history of any previous cancer, including solid tumors and hematologic malignancies. Data regarding the use of radiotherapy was reviewed. Information was analyzed using standardized incidence ratios (SIRs), defined as the ratio of observed to expected cases adjusted by person years at risk. SIRs are considered statistically significant if corresponding 99% exact confidence intervals (CIs) exclude 1.0. All results were standardized using a referent population matched to the index cases based on age, sex, race, and time period. Results: A total of 20,341 patients with secondary UBC were identified. A higher incidence in secondary UBC was seen amongst rectal, prostate cervical and uterine cancer patients receiving radiotherapy (see Table). Patients with lung cancer had a higher incidence of secondary UBC irrespective of radiotherapy use. Compared to patients with secondary UBC and no prior radiotherapy, patients with secondary UBC with prior radiotherapy had a higher rate of localized disease (79% vs 75%, P &lt; 0.0001) and had poorer survival on multivariate analysis (HR 1.06, 95%CI 1.05-1.06; P &lt; 0.0001). Conclusions: Patients with selected abdominal and pelvic tumors who received radiotherapy had a higher rate of secondary UBC. Further study is needed to determine whether these cancers represent a biologically distinct entity. [Table: see text]