tbuckley/cabot-search huggingface dataset:
A multicenter phase II study of irinotecan (CPT) and 5-fluorouracil (5FU)/l-leucovorin (l-LV) in patients with metastatic colorectal cancer: Interim results
Authors: H. Fujishima, K. Uchino, O. Miyanaga, A. Ueda, K. Miyazaki, H. Ariyama, E. Baba, K. Mitsugi, M. Harada, S. Nakano
Journal: Journal of Clinical Oncology (2004)

3667 Background:A previous phase I trial in 18 patients (pts) with metastatic colorectal cancer (CRC) demonstrated that weekly CPT and bolus 5FU/l-LV administered for 3 weeks every 28 days (modified Saltz regimen) had reduced toxicity without losing therapeutic efficacy, compared to original Saltz reigimen. The dose-limiting toxicity was limited to neutropenia, and a response rate of 39% and 44% stable disease could be achieved. Methods: In order to determine the effectiveness and tolerability of this regimen, we initiated a multicenter phase II trial applying the recommended weekly doses of CPT (100 mg/m2) and bolus 5FU (500 mg/m2) plus l-LV (20 mg/m2) administered for 3 weeks every 28 days. Pts with metastatic CRC, measurable disease, performance status ECOG less than 3, and adequate organ functions were eligible. Sixteen patients with metastatic CRC either previously treated with 5FU and LV (7 pts) or without previous chemotherapy (9 pts) were included and evaluated for response and toxicity. Results:In the 16 pts, there were 6 partial responses (37.5%) and 8 pts with stable disease (50%). The response rates of the pts with or without previous treatments were 14.3% and 55.6%, respectively. Median survival has not been reached. Similar to the results of phase I study, dose limiting toxicity in the phase II trial was neutropenia, with National Cancer Institute Common Toxicity criteria grade 3/4 in 50% of pts. Non-hematological toxicities were grade1/2 and included diarrhea, nausea, alopecia, and stomatitis. No treatment related death has been observed. Conclusions:This weekly CPT/5FU/l-LV administered for 3 weeks every 28 days has manageable toxicity and substantial anti-tumor activity, specifically for patients without previous chemotherapy. No significant financial relationships to disclose.
Association between the founder brazilian TP53 p.R337H mutation and HER2-positive status.
Authors: Juliana Giacomazzi, Marcia S. Graudenz, Cynthia ABT Osorio, Patricia Koehler-Santos, Edenir Inez Palmero, Rodrigo Augusto Depieri Michelli, Gabriela Carvalho Fernandes, Cristovam Scapulatempo Neto, Maria Isabel Waddington Achatz, Ghyslaine Martel-Planche, Fernando A Soares, Maira Caleffi, Jose Roberto Goldim, Pierre Hainaut, Suzi Alves Camey, Patricia Ashton-Prolla
Journal: Journal of Clinical Oncology (2013)

e22154 Background: Recent studies in North American and British series have suggested an association between germline TP53 mutations and early onset HER2-positive breast cancer (BC). Mutations in the TP53 gene are estimated to occur in 1:2,000-1:5,000 individuals of the general population. Among women with BC who are unselected for family history they occur in up to 0.25%. In women with early-onset BC (&lt;30 years) they occur in up to 7%. A specific germline TP53 mutation (c.1010G&gt;A; p.R337H) has been encountered in 0.3% of the general population, in 13.3% of Li-Fraumeni-like families and in 0.5-2.4% of BC-affected women in Brazil. In an exploratory approach, the aim of this study was to investigate, in our series, if there is an association between human epidermal growth factor receptor 2 (HER2) amplification and the germline TP53 p.R337H mutation in a series of BC-affected women. Methods: A series of 718 Brazilian BC-affected women was genotyped in our previous study and 64 (8.9%) were mutation carriers. These cases were recruited from 3 centers and HER2 analysis was performed by immunohistochemistry (IHC) in each center according to validated protocols. Statistical analysis was done using SPSS software. Results: In 47 of 64 mutation carriers (73.5%), BC showed HER expression (either 1+, 2+ or 3+) while among 654 non-carriers, this immunophenotype was observed in 320 (48.9%) (p&lt;0.001). This pattern was still observed after stratification of groups according to age at diagnosis (≤45 and ≥55 years) (p&lt;0.001 and 0.03, respectively) and was independent of recruiting center. Conclusions: These results indicate that BC developing on a background of the founder Brazilian TP53 p.R337H mutation shows more frequently some amplification of HER2, consistent with recent studies showing an association between germline TP53 mutations and BC with HER2 hyperexpression. These findings should be confirmed in larger series to understand the significance of the association. If confirmed, this finding may justify germline TP53 p.R337H mutation testing in all HER2-positive Brazilian BC patients and would have a significant impact on patient and family counseling as well as on treatment.
Measuring experiences of patients with cancer with care: The SEER-CAHPS linked data resource.
Authors: Erin Kent, Lisa M Lines, Sarah Gaillot, Nicola C. Schussler, Michael Halpern, Michelle Mollica, Maria Rincon, Ashley Wilder Smith
Journal: Journal of Clinical Oncology (2017)

238 Background: Care experience ratings are recognized as measures of quality. We introduce a new resource, SEER-CAHPS, linking cancer registry data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) program with Medicare claims and the Medicare Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey. Methods: The SEER-CAHPS data resource includes registry data from 1973-2011 (diagnosis, incidence, mortality, and sociodemographic data), Medicare CAHPS survey data from 1998-2013 (sociodemographic, health status, and care experience ratings), and Medicare fee-for-service (FFS) claims data from 2002-2013. SEER-CAHPS includes global ratings of overall care, personal doctor, specialist, health plan, and prescription drug plan and composite ratings of doctor communication, care coordination, getting needed care, and getting care quickly. The data also contain optional survey weights to account for the Medicare CAHPS sampling design. Results: Currently, SEER-CAHPS includes 205,339 individuals with a history of cancer documented in SEER (FFS: 26,802 with a survey before cancer diagnosis, and 55,231 with a survey after cancer diagnosis; Medicare Advantage [MA]: 57,227 with a survey before cancer diagnosis and 71,436 with a survey after cancer diagnosis). The database also includes 724,965 MCAHPS respondents without cancer in SEER regions (FFS: 282,592; MA: 447,358). The data provide insights on topics including experiences of cancer patients in their last year of life; experiences of cancer survivors; experiences of dually eligible (Medicare-Medicaid) cancer patients; and the associations of guideline-concordant follow-up care with patient experiences among people with colorectal cancer. We will demonstrate project sample-size estimation and present instructions for submitting data access applications. Conclusions: SEER-CAHPS provides population-based, cancer-specific data on patient experiences and associations with both health outcomes and healthcare utilization.
Reviewing systemic treatment regimens to reduce unintentional errors.
Authors: Andrea Crespo, Erin Redwood, Kathy Vu, Vishal Kukreti
Journal: Journal of Clinical Oncology (2017)

51 Background: Use of systemic treatment computerized prescriber order entry (ST CPOE) and pre-printed orders (PPO) are proven error reduction measures. Such systems are not failsafe, as regimen development depends on cognitive input at critical points and is susceptible to human error. No known guidance currently exists in oncology to ensure regimens are of high quality and built as intended. The purpose of this initiative was to improve the quality of oncology regimens in Ontario. Methods: A review of 35 centres, representing 75 treatment centres in a hub-and-spoke model, was conducted for all active regimens (PPO and CPOE) to ensure they were built as intended, with respect to drugs and doses. Centres completed an exploratory survey to report any unintentional discrepancies and existing maintenance review processes. The survey collected centre demographics and contained descriptive questions to document details of the regimen review and maintenance processes. Results: The review yielded an 86% response rate (12 regional and 18 community cancer centres). Upwards of 700 regimens were reviewed by a multidisciplinary team at each participating centre. Unintentional discrepancies were reported by 7 of the 30 (23%) centres (range of 2 – 141 per centre); types and examples are presented in the Table. Only 2 of 30 centres (7%) had an established regimen maintenance process. Conclusions: The review identified unintentional discrepancies and, due to the potential for patient harm, corrective action has been taken. There is a need for guidance and adoption of a standardized approach in order to sustain a high-quality regimen build and review process across the province. Consensus-based recommendations for ST CPOE and PPO regimen development and maintenance have been developed. Identified discrepancies have been amended and maintenance review processes are now implemented to improve the quality and safety of systemic treatment delivery. [Table: see text]
Out-of-pocket (OOP) health care expenditure burden for Medicare beneficiaries with cancer.
Authors: Ilene H. Zuckerman, Naimish B. Pandya, Bruce C. Stuart, Thomas Shaffer, Mujde Z. Erten, Xuehua Ke, J. Samantha Shoemaker, Ming-Hui Tai, Amy J. Davidoff
Journal: Journal of Clinical Oncology (2012)

6075 Background: Concern is increasing about the OOP burden faced by cancer patients (pts). Medicare beneficiaries have multiple comorbidities, have limited financial resources, and may face substantial cost sharing under traditional Medicare if they do not have generous supplemental coverage. We examined OOP spending and burden relative to income for Medicare beneficiaries with cancer, compared to a non-cancer comparison group. Methods: We used Medicare Current Beneficiary Survey data (1997-2007). Newly diagnosed cancer pts were selected using ICD-9CM codes on claims after a 12 mos washout period. OOP spending was assessed using self report for the index(diagnosis) and subsequent year. Pt characteristics were self reported. Generalized Linear Models estimated effects of pt characteristics on OOP spending; logistic regression identified pt characteristics associated with high burden, defined as OOP spending &gt;20% of income. Results: The cohort included 1,869 beneficiaries with, and 10,057 beneficiaries without cancer. Relative to the non-cancer cohort, cancer pts were older, had greater comorbidities, and were more likely to lack supplemental coverage (22 vs 16%) (all at p&lt;0.01).OOP spending was $4,727 or 11.4% of total spending for cancer pts. The unadjusted difference between cancer and non-cancer pts in OOP spending was $1,518 (p&lt;.001); with adjustment for patient characteristics, cancer patients faced an incremental $956 (p&lt;.01) in OOP spending. Median[mean] OOP/income was 10%[24%] for beneficiaries with, compared to 6%[14%] without cancer (p&lt;.001). Over ¼ (28%) of beneficiaries with cancer spent 20% of their income OOP, compared to 16% of beneficiaries without cancer (p&lt;.001). Supplemental insurance and higher income were protective against high OOP burden, whereas assets, comorbidity, and receipt of cancer-directed radiation and antineoplastic therapy were associated with higher OOP burden. Conclusions: Medicare beneficiaries with cancer face higher OOP burden than their counterparts without cancer; some of the higher burden was explained by higher comorbidity burden and lack of supplemental insurance. Financial pressures may discourage some elderly patients from pursuing treatment.
The pharmacokinetics and pharmacodynamics of docetaxel (DCTX) in Caucasian and African American patients with solid tumors
Authors: L. D. Lewis, G. L. Rosner, A. A. Miller, M. J. Egorin, M. V. Relling, H. Kastrissios, R. Bies, M. J. Ratain
Journal: Journal of Clinical Oncology (2004)

2043 Background: Increased oral clearance (CL/F) of drugs that are CYP3A and/or P-glycoprotein (P-gp) substrates has been reported in African-American (AA) compared to Caucasian (C) patients (pts). The primary study objective was to test the hypothesis that the pharmacokinetics and pharmacodynamics of DCTX, an intravenously administered substrate for CYP3A and P-gp, would be different between C and AA pts. Methods: DCTX population pharmacokinetics and pharmacodynamics were studied following a single intravenous dose of DCTX (75 or 100 mg/m2) in cancer pts. of C and AA ethnicity. Timed blood samples, using a published limited sampling regimen, were obtained. Clinical toxicity and absolute neutrophil count (ANC) were monitored on days 8, 15 and 22 post treatment. DCTX concentrations were measured by HPLC. A complete population pharmacokinetic analysis is being performed and genotyping for CYP3A and P-gp is ongoing using sequencing or polymerase chain reaction -restriction fragment length polymorphisms (PCR-RFLP). Results: 109 pts were enrolled into the study. There were 69 C (43M:26F) median age 61 yr (range 29–73) and 40 AA (26M:14F) median age 63 yr (range 38–81). Mean ± SD DCTX Cmax and C6h (all adjusted to 75 mg/m2dose) are shown in the table below. There was no difference in the percent reduction in ANC from baseline (mean ± SD; n) between C (81± 19%; n=43) and AA (75± 24%; n=20) when patients who received 75 mg/m2 DCTX were compared. Relationships between DCTX pharmacokinetics and CYP3A and P-gp genotype in the two ethninc groups are being explored. Conclusions: There was no apparent difference in DCTX pharmacokinetics or DCTX induced myelosuppression between cancer patients of either C or AA ethnicity. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis
Identifying cancer quality measurement gaps in the Choosing Wisely Initiative.
Authors: Kelsey Corrigan, Sarvesh Agarwal, Leonid Aksenov, Alexandra Paul, Banafsheh Sharif-Askary, Arif Kamal
Journal: Journal of Clinical Oncology (2017)

7 Background: Cancer is a leading cause of morbidity in the US. Improvements in treatment strategies are rapidly transitioning many cancers into long-term, chronic illnesses, similar to heart failure, COPD, and diabetes. We compared the prevalence and focus of cancer and non-cancer quality measures within the Choosing Wisely Initiative to assess possible measure gaps. Methods: The Choosing Wisely Initiative is the most recognized public campaign to reduce low value services in health care. We identified all published Choosing Wisely measures from April 2012 to May 2016 and abstracted for target disease, care setting, type of care, and patient age. We calculated descriptive statistics and chi-squares for analysis. Results: 75 healthcare organizations submitted 461 total Choosing Wisely measures. Of these, 15% (71/461) involved cancer and 15% (68/461) involved non-cancer chronic illnesses, including heart disease, diabetes, COPD, asthma, stroke, and Alzheimer’s Disease; 70% (322/461) were “other”. Among measures, 30% (139/461) overlapped between cancer and non-cancer chronic illnesses. Among cancer measures, a minority (10/71; 14%) were submitted by ASCO. Prostate cancer (28%) and breast cancer (23%) were the two most addressed cancer diagnoses. Among cancer guidelines, 79% (66/84) targeted imaging, tests, and/or procedures, 12% (10/84) addressed treatment, 5% (4/84) addressed medications, and 5% (4/84) targeted prevention. This is similar to non-cancer chronic illnesses, which had 72% (60/83) of guidelines targeting imaging, tests, and/or procedures, 13% (11/83) of guidelines addressing treatment, 8% (7/83) addressed medications, and 6% (5/83) targeted prevention. In examining numbers of measures per prevalence of the diseases addressed, we found 71 guidelines for 14.4 million people for cancer and 68 guidelines for 152 million people with non-cancer chronic illnesses (p&lt;0.001). Conclusions: Quality measures involving serious illness, including cancer, represent a minority of the Choosing Wisely measures. Existing quality measures emphasize diagnostics and procedures. Future measures should target the chronic illness aspects of cancer care, including prevention, survivorship, and palliative care.
Racial disparity in diffuse large B-cell lymphoma survival.
Authors: Xuesong Han, Ahmedin Jemal, Elizabeth M. Ward
Journal: Journal of Clinical Oncology (2013)

6569 Background: Although blacks have a lower risk of non-Hodgkin lymphoma (NHL) compared to whites, black non-Hodgkin lymphoma (NHL) patients experience worse survival than white patients. This study aims to examine in patients with diffuse large B-cell lymphoma (DLBCL), the most common subtype of NHL, how much of the racial disparity in survival can be explained by differences in certain demographic (age, sex and area-level education) and access-to-care-related (stage, treatment, health insurance status) factors. Methods: Our cohort included 3716 non-Hispanic white or black DLBCL patients aged 18-64, diagnosed in 2004-2005 from the National Cancer Database (NCDB), a nationwide, hospital-based cancer registry. The analysis included only HIV/AIDS-negative patients. Kaplan-Meier survival curves were drawn for blacks and whites. Cox proportional hazards model was fitted to estimate hazard ratios (HR) and the 95% confidence intervals (CI) for race with and without controlling for demographic factors (age, sex and area-level education), stage, treatment and health insurance status. Results: Black patients had a worse survival than white patients (5-year survival rate 66.6% in blacks vs. 73.3% in whites, log-rank test p-value = 0.0006). Without adjusting for other factors, blacks had a 34% higher risk of death compared to whites (crude HR=1.34, 95% CI =1.13-1.58). After adjusting for demographic factors including age, sex and area-level education, the HR reduced to 1.27 (95% CI=1.06-1.51). After further adjustment for stage, treatment and insurance status, the association disappeared (HR=1.03, 95% CI= 0.86-1.23). Conclusions: Demographic factors and access-to-care-related factors including stage, treatment and health insurance status fully explained the black-white racial disparity in DLBCL survival in this cohort. Our findings suggest that improvements towards timely diagnosis, appropriate treatment and other adequate access to health care measures could potentially eliminate the survival disparity between black and white DLBCL patients.
Risk factors for ovarian cancer: Is there a missing link?
Authors: S. Sadetzki, F. Modugno, B. Oberman, A. Chetrit, F. Lubin, R. Ness
Journal: Journal of Clinical Oncology (2004)

5012 Background: Despite the higher prevalence of BRCA1/2 mutations among Ashkenazi women, ovarian cancer (OvC) incidence among European-American Israeli women is similar to that of Caucasians in the US. Three hypotheses may explain this observation: either Israeli women practice more protective behaviors or Americans are more exposed to risk factors. Alternatively, due to gene-gene or gene-environment interactions, risk factors might affect each population differently. Finally, unidentified risk factors may differ between these populations. Methods: We compared the magnitude and effects of OvC risk factors between Israeli-Jewish and US Pennsylvania women using data from two population-based case-control studies conducted in the 1990s. The Israeli study included 998 cases and 1528 controls individually matched by age and ethnicity. The American group comprised 767 cases frequency matched by age and race to 1367 controls. Both studies used personal interviews to obtain risk factor data. Odds ratios (ORs) adjusted for age, education and race/origin were calculated using logistic regression and compared by Walds Test. Results:Significant differences in the distribution of most study variables were found between the two groups. Israeli women reported more positive family history of OvC, a later age at menarche and menopause, less nulliparity, more livebirths and longer duration of breastfeeding. Oral contraceptive (OC) use and tubal ligation, were significantly more prevalent among US women. Both studies showed consistent results regarding the role of most factors on OvC risk. However, the protective role of OC use and parity was more pronounced in the US (OC use 5+ years vs. never OR= 0.84 and 0.6, p=0.14; livebirth 3+ vs 0 OR= 0.52 & 0.27, p=0.02, Israeli and American groups, respectively). Conclusions: Considering the higher prevalence of genetic risk factors in the Israeli population together with the increased protection for OC use and parity among US women, a modification effect of BRCA1/2 mutations on these factors might exist. Otherwise, these findings might indicate the presence of other unidentified environmental and/or genetic factors that provide increased protection to Israeli women. No significant financial relationships to disclose.
Dynamic contrast enhanced MRI detects changes in vascular transport rate constants following treatment with thermally-sensitive liposomal doxorubicin
Authors: Brett Z. Fite, Azadeh Kheirolomoom, Josquin L. Foiret, Jai W. Seo, Lisa M. Mahakian, Elizabeth S. Ingham, Sarah M. Tam, Alexander D. Borowsky, Fitz-Roy E. Curry, Katherine W. Ferrara
Journal: Journal of Controlled Release (2017)
EGFR mutation rate in liquid-based cytology compared with biopsies from primary and metastatic lung cancer using real-time PCR.
Authors: Simonetta Buglioni, Valerio D'Alicandro, Elisa Melucci, Cristiana Ercolani, Paolo Visca, Alessandra Fabi, Massimo Filippetti, Michele Milella, Marcella Mottolese
Journal: Journal of Clinical Oncology (2013)

e19052 Background: Specific EGFR tyrosine kinase inhibitors (TKIs) are recommended as first-line therapy in patients with non-small cell lung cancer (NSCLC) that have active EGFR mutations. Although cytology and tumor biopsy are a very common approaches to evaluate patient eligibility to TKIs, the limited number of tumor cells present in these samples may often constitute a bias for molecular analysis. In this context, the use of sensitive methods to detect EGFR mutations may be of pivotal clinical importance. The aim of this study was two-fold: 1) to determine the accuracy and sensitivity in detecting EGFR mutations between liquid-based cytology (LBC) and bioptic specimens, 2) to compare the performance of direct DNA sequencing and real-time PCR (qPCR) in two different series of cytologic and histologic primary and metastatic NSCLC. Methods: DNA wasextracted from 537 specimens of NSCLC patients including 422 biopsies and 115 ThinPrep (TP) collected samples respectively. EGFR mutations were analyzed by direct sequencing (exons 19 and 21) in 284 biopsies and 68 TP samples and by qPCR (exons 18, 19, 20, 21) in 138 biopsies and 47 LBC samples. Results: The overall specimen insufficiency rate between LBC and biopsies was significantly higher by direct sequencing compared to qPCR (biopsies: 11.6% vs 7.2%) and (LBC: 14.7% vs 2.3%). In the series of 309 valuable cases analyzed by direct sequencing (251 bioptic and 58 LBC), we found 34 (11%) EGFR mutations (11.2% biopsies and 10.3% LBC ). Of interest, a higher percentage of EGFR mutant cases (18.1%) was observed in the 170 valuable cases analyzed by qPCR (11.1% biopsies and 21.4% LBC). Conclusions: Our data indicate that TP collected specimens seem to be more reliable than formalin fixed biopsies for molecular analysis, probably due to the better quality of the extracted DNA. Furthermore, qPCR enabled detection of EGFR mutations in samples with low tumor content for which conventional Sanger sequencing was not informative.