bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effective treatment of triple-negative breast cancer with targeted cytotoxic somatostatin analogue AN-162 (AEZS-124)
Authors: Seitz S. , Schally A. V. , Gluck S. , Rick F. , Szalontay L. , Hohla F. , Papadia A. , Köster F. , Ortmann O. , Buchholz S. 
Published: August 2020

619 Background: Triple negative breast cancers (TNBC) represent a distinct subtype of breast cancer being negative to ER, PR and HER2 and are associated with poor prognosis. Limited systemic treatment options exist for TNBC. TNBC cells express somatostatin receptors (SSTR). Therefore, to investigate preclinical characteristics of TNBC we used a novel targeted cytotoxic somatostatin analogue AN-162 containing doxorubicin (DOX) which binds to the subtypes 2, 3 and 5 of SSTR. Methods: The expression of SSTR in HCC 1806 human TNBC cell line was detected by RT-PCR. Cytotoxic effect of AN-162 in vitro was visualized by ethidium bromide staining fluorescence microscopy. Internalization of AN-162 into HCC 1806 cells was tested by 125Iodide-labeled AN-162 uptake assays and the presence of DOX in the nucleus was measured by fluorescence assays after separating the nucleus from the cytoplasm. For in vivo experiments, HCC 1806 TNBC cells were xenografted subcutaneously into nude mice which were then randomized into four groups receiving AN-162, DOX, an unconjugated mixture of DOX and somatostatin analogue RC-160 at the same equimolar dose of 2.5 μmol/kg (1.45 mg/kg Dox equivalent) i.v. (q7d 4x) and vehicle solution control. Results: HCC 1806 TNBC cell line was positive for the expression of all five SSTR receptor subtypes. Ethidum bromide staining of cells treated with 2.5 μM of AN-162 for 30 min demonstrated cell death after 24h by fluorescence microscopy. Uptake assays with AN-162 showed specific internalization of AN-162 into the cells mediated through the sstrs. After treatment of the cells with 2.5 μM AN-162 for 10 or 30 min, DOX could be detected in the nucleus by fluorescence assays. In vivo, AN-162 significantly (p<0.05) inhibited tumor growth of HCC 1806 xenografts compared to Control, DOX and the unconjugated mixture of DOX+RC-160 from day 14 and the inhibition remained significant until the end of the study on day 35. Conclusions: Our results indicate that treatment with targeted cytotoxic somatostatin analogue AN-162 produces a greater inhibition of tumor growth than DOX alone in somatostatin receptor positive TNBC. Our findings support the concept of targeted chemotherapy based on cytotoxic peptide analogues for the treatment of breast cancer and other cancers. No significant financial relationships to disclose.
Effect of modest delays in primary surgical treatment on progression of tumor size in breast cancer patients
Authors: Wagner J. L. , Warneke C. , Bedrosian I. , Mittendorf E. , Babiera G. , Kuerer H. , Hunt K. , Yang W. , Sahin A. , Meric-Bernstam F. 
Published: August 2020

622 Background: Evaluation of medical co-morbidities, coordination of reconstructive surgery and referral to tertiary care centers can delay surgical treatment in breast cancer. These delays raise concerns for tumor progression in the interim. We evaluated the time from initial imaging at a cancer center to surgical treatment and the change in tumor size. Methods: We identified 823 patients who underwent surgery as their first therapeutic modality for invasive breast cancer diagnosed from December 2003 to September 2005. Baseline tumor size was determined by mammogram (MMG) and ultrasound (US) reports, and tumor size at surgery was determined by pathology reports. Results: The median time from imaging at our facility to surgery was 0.69 months (range 0.03 to 4.34). Multivariate modeling indicated that older patient age, undergoing total mastectomy, and undergoing reconstruction predicted a longer time from initial imaging to surgery. Comparing radiographic to pathologic size, a moderate correlation was demonstrated for both MMG (Spearman r = 0.58; p < 0.0001) and US (Spearman r = 0.66, p < 0.0001). Pathologic size was the same as MMG size in 14%, smaller in 49%, and larger in 37% of patients. Differences in tumor size estimates were not significantly associated with time lapse between MMG and surgery, but in a multivariate model, MMG tumor size, tumor histology, and tumor grade were significant predictors (p < 0.0001 for all) of differences in mammographic and pathologic size. The pathologic tumor size was the same as US in 10%, smaller in 38%, and larger in 52% of patients. Time lapse to surgery was not significantly associated with differences in US and pathologic tumor size. In a multivariate model, US tumor size (p < 0.0001), tumor histology (p = 0.0006) and tumor grade (p = 0.005) were significant predictors of differences in US and pathologic tumor size estimates. Conclusions: There is no evidence that time lapse from initial imaging to surgical intervention leads to significant changes in tumor size thus allowing patients to complete preoperative workup and planning without significant clinical disease progression. No significant financial relationships to disclose.
The utility of a real-time RT-PCR assay for the detection of metastases greater than 0.2 mm in sentinel lymph nodes of breast cancer patients confirmed by detailed histological analysis
Authors: Kurosumi M. , Kobayashi Y. , Takei H. 
Published: August 2020

628 Background: Analysis using real time RT-PCR for the detection of metastases in lymph nodes (LN) increases sampling but is associated with a risk of too much sensitivity as compared to histological analysis. Determining the appropriate cutoff value is important in introducing this system to routine clinical practice. Our study confirms the reliability of the cutoff values of a real-time RT-PCR assay (GeneSearch, Veridex LLC) to detect metastases larger than 0.2 mm by detailed 0.2 mm frozen section histological diagnosis. Methods: 129 sentinel and non-sentinel lymph nodes were obtained by sentinel LN biopsy from 79 breast cancer patients. All LNs were cut in half. One half of each LN was used for routine intra-operative diagnosis. The other LN half had sections cut every 0.2 mm for histological analysis. All frozen sections were H&E stained and examined by on-site pathologists. These sections were then re-stained immunohistochemically using a pancytokeratin antibody (AE1/AE3) for detecting submicrometastses. All remaining tissue between the histology sections was assayed by the real-time RT-PCR assay using the genetic markers mammaglobin (MG) and cytokeratin-19 (CK-19) (note: tissue processing method was investigational and off-label). Cutoff values were pre-set in a large US study (n = 304). Results: Compared to the histological diagnosis using 0.2 mm interval frozen sections, the real-time RT-PCR results were as follows; sensitivity of 100.0% (34/34), specificity of 93.7% (89/95), and overall accuracy of 95.3% (123/129). Submicrometastases were recognized by IHC in 3 of 95 samples (2 solitary and 1 multiple sites) diagnosed as negative by H&E-stain sections, and 3 samples were negative for RT-PCR. Conclusions: Results of 0.2 mm interval histological analysis suggest a near perfect sensitivity of the real time RT-PCR assay, allowing reliable detection of LN metastases larger than 0.2 mm. In addition, at least three samples with submicrometastases detected by immunohistochemistry for pancytokeratin were above the preset cutoff values of this real time RT-PCR assay. [Table: see text]
Does it matter where you go for breast cancer surgery?
Authors: Hofer T. P. , Hawley S. T. , Katz S. J. 
Published: August 2020

6504 Background: Variation in receipt of local therapy for breast cancer has motivated research addressing whether treatment differences are attributable to surgeons. We assessed the amount of variation in receipt of mastectomy and breast reconstruction attributable to surgeons and evaluated patient and surgeon factors associated with treatment variability. Methods: Women with non-metastatic breast cancer aged 20–79 diagnosed from June 2005-February 2007 in Detroit and Los Angeles were surveyed after surgical treatment (response rate 72%, N = 2,260). Attending surgeons were surveyed (response rate 76.1%, N = 318). Patient and surgeon data were merged to SEER data (1764 patients and 295 surgeons). Two dependent variables were receipt of mastectomy and reconstruction. Patient variables were age, ethnicity, marital status, tumor size, behavior, and grade. Surgeon factors included age, gender, years in practice, percent of total practice devoted to breast cancer, hospital setting, and 3 scales measuring patient management processes. We used separate random effects models for each dependent variable to determine the amount of treatment variation attributable to surgeons and the amount of within-surgeon variability explained by patient and surgeon factors. Results: The number of patients per surgeon ranged from 1 to 35 (mean 5.5). One-third of women received mastectomy, 30% of whom received reconstruction. The amount of variation in mastectomy attributable to individual surgeons was moderate (8%, median odds ratio 1.7). Patient factors explained half this variation, while surgeon factors explained very little (<1%). The amount of variation in reconstruction attributable to individual surgeons was large (18%, median odds ratio 2.3), with patient level factors explaining one third of this variation. One surgeon level factor (propensity to refer to a plastic surgeon prior to surgery) explained an additional third of the variance. Conclusions: These results suggest that individual surgeons and their attributes contribute only modestly to the variation in primary surgery for breast cancer. By contrast, individual surgeons play a much larger role in explaining the wide variation in receipt of breast reconstruction- primarily through preoperative referral to plastic surgeons. No significant financial relationships to disclose.
The impact of socioeconomic status (SES) on stage of cancer at time of diagnosis: A population-based study in Ontario, Canada
Authors: Booth C. M. , Li G. , Mackillop W. J. 
Published: August 2020

6505 Background: Lower SES is known to be associated with worsened cancer survival. Here we evaluate the impact of SES on stage of cancer at diagnosis in Ontario which has universal health insurance. Methods: All incident cases of breast, colon, rectal, non-small cell lung, cervical and larynx cancer diagnosed in Ontario 2003–2005 were identified using the Ontario Cancer Registry. Stage information is only captured routinely for patients seen at Ontario's 8 Regional Cancer Centers (RCCs). This represents approximately 68% of the population and forms the basis for all analyses. Using a best stage grouping approach, cases were assigned stage based on pathologic TNM if available and clinical TNM otherwise. The population of Ontario was divided into quintiles based on community median household income reported in the 2001 Canadian census. Using postal code at time of diagnosis cases were assigned to quintiles (Q); Q1 represents the communities where the poorest 20% of the Ontario population resided. Comparisons between Q1 and Q2–5 were made using the chi-square test. A Cox model was used to evaluate overall survival, SES, stage, and age. Results: Stage at diagnosis was available for 19,239/23,254 (83%) of cases seen at RCCs. Among cases with breast cancer, those in Q1 were less likely to have stage I disease (43 vs 47%, p = 0.004) and more likely to have stage IV disease (5 vs 4%, 0.008) than Q2–5. With lung cancer, cases in Q1 were more likely to have stage I disease compared to Q2–5 (16 vs 13%, p = 0.015). Distribution of stage I and stage IV disease did not differ by SES across other individual diseases. However, for all 6 cancers combined, cases in Q1 were less likely than Q2–5 to have stage I disease (27 vs 30%, p = 0.001) and more likely to have stage IV disease (21 vs 18%, p < 0.0001). We found significant gradients in 3-year overall survival across Q1-Q5 for breast (5% absolute difference in survival, p < 0.001), colon (4%, p = 0.049), and cervical (18%, p = 0.031) cancers. Adjustment for stage and age only slightly diminished these survival gradients. Conclusions: Despite universal health care, SES remains associated with survival among patients with cancer in Ontario. These data suggest that the difference in outcome is only partially explained by differences in stage at diagnosis. No significant financial relationships to disclose.
The access to oncology drugs in France, Germany, Italy, Spain, and the United Kingdom: A comparison based on data from 1998 to 2007
Authors: Wilking N. E. , Jönsson B. 
Published: August 2020

6525 Background: Drugs constitute a key element in the treatment of solid tumors and in haematology. We have analysed the access and uptake of oncology drugs in 27 countries over a 10 year period (1998–2007) based on sales data provided by IMS Health ( www.comparatorreports.se ). Methods: In this special analysis we study a set of “mature” cancer drugs ( irinotecan, aromatase inhibitors (AIs), oxaliplatin, docetaxel, rituximab, gemcitabine, trastuzumab and imatinib) available in 2002 or before and a set of “new” cancer drugs (bortezomib, cetuximab, bevacizumab, pemetrexed, erlotinib, sorafinib, sunitinib and dasatinib) available in 2003 or later. The “mature” drugs have been selected based on the fact that they have been available for a long period of time (at least 5 years) and that there is accumulated evidence based on clinical trials, epidemiological studies and clinical experience that they have had a major and clinically relevant impact on the outcome in different areas of oncology. Results: We see very different patterns of use in countries studied. The total use of cancer drugs (€/capita) in 2007 is highest in France and lowest in the UK, with the other countries at a relatively similar level in between. The pattern of use of “new drugs” follows that of “mature drugs”, but the very low use of new drugs in UK is noticeable. The differences seen between groups are also reflected in the use of individual drugs, although for example AIs and trastuzumab in the “mature” group have a more uniform use across the countries. The expected survival for cancer patients have been, in general, lower in the UK compared to other western European countries, but further studies are needed to establish the impact of treatment patterns on population outcome. Conclusions: The similarity in use of both “mature” and “new” oncology drugs indicate that differences in access, found for example between France and UK, is related to health care system factors rather that evidence on outcome of use of the drugs. [Table: see text] [Table: see text]
Breast cancer patients' quality of care: Does racial concordance matter or is it just a matter of trust?
Authors: Joseph K. P. , Franco R. , Fei K. , Bickell N. 
Published: August 2020

6537 Background: As insurers consider paying for performance and quality measures grow in importance, factors that affect patients' perceived quality of cancer care matter. Concordance by race in physician-patient relationships has been associated with patient satisfaction and use of health care, however how that is mediated is unclear. Methods: 210 of 300 eligible women stage I or II breast cancer at 1 of 8 participating NYC hospitals responded to our survey (70% response rate): 20% were African-American (AA), 40% were white, and 30% were Hispanic and 9% were other races. Trust is based on a validated scale and calibrated to a 100 point scale (Cronbach α = 0.76). Bivariate analyses and logistic models were used to identify factors associated with patient ratings of quality of care. Results: Only 55% of women rated the quality of their cancer care as excellent. AA women breast cancer patients were less likely to rate their care as excellent (p=0.004). Compared to women who didn't rate their care as excellent, those who rated it excellent had greater trust in their physician (p < 0.0001) and indicated that were treated well by their physicians' office staff (p = 0.01). Of note, AA patients had lower levels of trust (p = 0.004). Women who were of the same race as their physician did not perceive better quality of care as compared to those who were not racially concordant (p = 0.18); nor did they have higher trust in their physician (p = 0.59). Multivariate models evaluating the role of patient race, education, income, knowing which physician to talk to, how well the staff treated the patient, and racial concordance with physician, found that trust in physician was significantly associated with patient perception of excellent quality care (aRR = 1.38; 95%CI: 1.03–1.65) and being AA was associated with worse perceived quality (aRR = 0.47; 95%CI: 0.21–0.88) (model c = 0.79; p < 0.0001). Conclusions: Racial concordance between physicians and patients does not directly affect patients' perceived quality of care. However, women's trust in their physician and their perceived treatment by office staff are associated with excellent cancer care quality ratings. Efforts should be made to increase effective intercultural communication particularly among AA women in order to improve ratings of cancer care quality. No significant financial relationships to disclose.
Randomized clinical trial eligibility rates for chemotherapy (CT) and antiangiogenic therapy (AAT) in a population-based cohort of newly diagnosed non-small cell lung cancer (NSCLC) patients
Authors: Fehrenbacher L. , Ackerson L. , Somkin C. 
Published: August 2020

6538 Background: NSCLC leads the US in cancer deaths, but randomized clinical trials (RCT) of CT with/without antiangiogenic therapy (AAT) are relatively slow to accrue. Treatment guidelines for NSCLC are based on RCTs that enroll patients with a mean age of 62–64 without serious comorbidities. SEER mean age of NSCLC diagnosis in the US is 70. Methods: 326 consecutively diagnosed (from January 1, 2006) NSCLC patients from a large prepaid health care delivery system (Kaiser Permanente Northern California-KPNC), were retrospectively evaluated by manual chart and electronic medical record review for eligibility criteria (EC) to enter treatment defining RCTs, i.e. E4599, S0023. The KPNC members are representative of the regional population. Ineligibility, the main endpoint, was determined on imaging and laboratory tests and history in the medical record. This may overestimate eligibility. Results: Age at diagnosis:<60years-18%, <65–28%, <70–50%, >75–34%, >80–18%; mean (SD)age- 69.3 (10.6). Male:Female 51:49%. Adeno-49%; Squamous-22%; LargeCell-2.5%; NSC NOS-27%. Current/former smokers-90%. Staging: IA-14%; IB-13%; IIA+B-4%; IIIA-17%; IIIB+IV-52%. Surgical resection-26%. When standard RCT eligibility criteria were applied to the entire cohort, 34% (CI 29%-39%) were eligible. Only 23% (CI 19%-28%) were both eligible and <75yo. stage IIIB+IV patients were 29% (CI 24%-36%) eligible at all ages, 20% (15%-26%) were both eligible and <75yo. When AAT EC were added, 21% (17%-26%) were eligible for all ages, 14% (CI 10%-18%) eligible and <75yo., and 9%(CI 6%-13%) eligible and <70yo. Conclusions: Treatment guidelines for NSCLC are based on RCTs enrolling the healthiest quartile of the youngest half of patients. The majority of NSCLC patients are excluded by trial eligibility criteria or subjective age criteria from entering CT and/or AAT RCTs. Toxicities in these older and more comorbid NSCLC patients likely alter the risk:benefit ratio. RCTs specific for the 70+yo and comorbid NSCLC patients are needed to help define the best therapy for this understudied majority of lung cancer patients. No significant financial relationships to disclose.
Interpreting out-of-pocket expenditures for cancer patients: The importance of considering baseline household income information
Authors: Oatis W. S. , Nonzee N. , Markossian T. , Shankaran V. , McKoy J. , Evens A. , Gordon L. , Winter J. , Calhoun E. , Bennett C. L. 
Published: August 2020

6541 Background: Few studies have examined cancer-related out-of-pocket costs (expenses resulting from cancer morbidity and treatment that are not covered by insurance) as a function of baseline household income. We report income-adjusted out-of-pocket cost ratios for 50 patients with lymphoma and 156 patients with breast cancer. Methods: Patients with lymphoma or breast cancer provided 3-month retrospective documentation of cancer-related out-of-pocket costs. Costs were adjusted for income by dividing monthly costs by monthly household income. Direct medical costs include costs related to medications, doctor visits, and hospital stays. Direct non-medical costs are cancer-related peripheral costs, such as transportation and meals. Indirect costs are costs due to lost income. Results: Of our study patients, 83% were Caucasian, 65% were married, 53% were employed, and 65% had at least a bachelor's degree. All patients were undergoing active treatment and had insurance. Mean monthly out-of-pocket costs for patients with lymphoma were slightly greater than for those with breast cancer ($1,888 vs $1,455, respectively). Among patients with an annual income of $30,000 or less, the total monthly out-of-pocket costs were more than 3 times the monthly household income for patients with lymphoma and equal to the monthly household income for patients with breast cancer. The total mean income-adjusted cost ratio was 1.75 for patients with aggressive non-Hodgkin lymphoma versus 0.42 and 0.61 for those with indolent non-Hodgkin lymphoma or Hodgkin disease, respectively. Conclusions: Cancer-related out-of-pocket expenses disproportionately affect lower-income individuals with lymphoma or breast cancer and are primarily driven by the financial burden of co-payments for medical care. Future studies should evaluate out-of-pocket costs in relation to household income to determine more accurately the economic burden of cancer. [Table: see text] No significant financial relationships to disclose.
The validity of cause of death coding within the Surveillance, Epidemiology, and End Results (SEER) Registry
Authors: Hu C. , Xing Y. , Cormier J. N. , Chang G. J. 
Published: August 2020

6544 Background: Disease-specific survival (DSS) analysis within large cancer registries is more informative than other methods of survival analysis but requires accurate information regarding the cause of death (COD). The purpose of this study was to evaluate the validity of the COD code for patients diagnosed with colon cancer and the extent to which it varies with regard to age, sex, and race within SEER. Methods: Patients with colon adenocarcinoma were identified from SEER (ver. 2008) from 1988 to 1998 to have at least 7 years of follow-up. Relative survival (RS) was calculated matching for age, sex, and the year of diagnosis using U.S. life-tables. Colon cancer cause of death was then assigned using SEER COD recode for colon and rectal death (21040–50). The number of observed and expected deaths by year was calculated to estimate deaths attributable to colon cancer. The ratio of this number to the recorded cause of death was defined as the validity of the COD code in SEER. Results: 86,641 patients were identified. Relative survival declined during the first 7 years of observation but then leveled indicating a minimum number of deaths subsequently attributable to colon cancer. At year 7 the observed number of deaths for the SEER cohort was 49,104; the expected number of deaths using life tables was 17,173. The difference (31,931) is theoretically attributable to colon cancer. Within the SEER cohort, 30,227 deaths were coded colorectal cancer deaths, an estimated validity of 94.6%. Stratified results demonstrated validity was sensitive to race but not age or gender (table). Conclusions: Cause of death coding for colon cancer in SEER is highly valid, suggesting that the use of DSS for colon cancer is appropriate. [Table: see text] No significant financial relationships to disclose.