bluuebunny/crossref_metadata_2025_split huggingface dataset:
TP53 status is an important prognostic marker for patients with hepatic metastases from colorectal carcinoma
Authors: Mollevi D. G. , Serrano T. , Ginesta M. M. , Valls J. , Torras J. , Ramos E. , Germà J. , Moreno V. , Capella G. , Figueras J. , Villanueva A. 
Published: March 2020

10092 Background: The aim of this study was to analyze the value of TP53 gene mutations as a prognostic marker to improve the selection of patients candidates to surgery in a consecutive series of liver metastases from colorectal cancer patients. Methods: 91 patients with liver metastases from colorectal carcinoma (CRC) were included. Mutational study of TP53 gene, exons 4 to 10, was assessed both in paraffin-embedded hepatic metastasis and normal liver parenchyma by SSCP (Single Strand Chain Polymorphism) followed by sequencing of abnormal electrophoretic mobility patterns. Immunostaining of P53 and P21 proteins were assessed in the same group of patients. Results: Forty-eight out 91 (50.05%) metastases showed mutation in TP53. Higher incidence of mutations was detected in exons 5–8, although exons 9 and 10 were mutated in 28.26% of metastases. Protein-truncating mutations (nonsense and frameshift) occur in 47.8% of metastasis harboring TP53 mutations. TP53 mutation was associated with poor prognosis in univariate (P=0.0062) and multivariate Cox proportional hazard model (P=0.012) analysis. Prognosis association was maintained in the group of patients undergoing radical resection, named R0 series (n=79; P=0.008). High prevalence of TP53 mutations happen in patients with >3 metastases (65.6%; P=0.034), primary tumors Duke’s C-D stages (57.4%; 63.0%; respectively; p=0.026) and patients with age <57 years at resection. Interestingly, patients with TP53 mutations in their metastases relapsed earlier after the resection of the primary tumor (P=0.026). Postoperative 5-FU-based chemotherapy showed a better survival outcome in patients with wild-type TP53 hepatic metastases (HR: 2.92; 95% CI: 1.32–6.46; P=0.006). Conclusions: TP53 mutational status seems to be an important prognostic factor in patients with hepatic metastases from CRC. No significant financial relationships to disclose.
ErbB3, Cyclin D1 and Ki67 nuclear staining predicts biochemical recurrence in prostate cancer treated by radical prostatectomy
Authors: Koumakpayi I. H. , Gannon P. O. , Le Page C. , Alam-Fahmy M. , Madore J. , Mes-Masson A. , Saad F. 
Published: March 2020

10096 Background: The nuclear accumulation of growth factor receptor was reported to be associated to increased cell proliferation. Cyclin D1 and Ki67 are nuclear markers of cell proliferation. Deregulation of Cyclin D1 and Ki67 expression play a role in tumorigenesis and metastasis. Recently, we observed that nuclear localization of ErbB3 was associated with prostate cancer progression. The objective of this study was to determine if the association of cell proliferation markers and nuclear localization of ErbB3 could predict biochemical recurrence (BCR) in patients with prostate cancer following radical prostatectomy. Methods: Using immunohistochemistry we analyzed a tissue microarray containing 386 cores from 64 formalin-fixed paraffin embedded specimens from prostate cancer patients who had undergone radical prostatectomy. No patient had received hormone therapy prior to surgery and prior to BCR. Antibodies against Cyclin D1, ErbB3 and Ki67 proteins were used. Results: Nuclear staining was 60%, 67% and 86% for Cyclin D1, ErbB3 and Ki67 respectively. In our cohort, 29 of 64 PCa patients (45%) had a BCR after a median 3 years of follow-up. Thirty seven (37) percent of patients had positive nuclear staining for all three markers. BCR free survival probability at 3 years was not significant for each marker individually, except for ErbB3 in positive surgical margin patients. When all three markers were combined for nuclear staining Kaplan-Meier analysis BCR free was 0.4 and 0.1 for positive and negative nuclear staining respectively (p=0.0068). Univariate COX regression analysis shows a 2.98 fold (95% CI: 1.29 - 6.86, p=0.01) higher rate of BCR in patients positive for these three markers. In addition, in a multivariate model, including pre-operative PSA (p=0.19), pathologic stage (p=0.29), Gleason grade (p=0.40) and specimens that had positive nuclear staining for the 3 markers were associated with a 3.97 fold higher rate of BCR (95% CI: 1.54 - 10.25, p=0.0068). Conclusion: These results suggest that the association of cell proliferation markers and nuclear localization of ErbB3 could be useful in predicting recurrence following radical prostatectomy and guide therapeutic decisions. Large scale trials are needed to confirm these results. No significant financial relationships to disclose.
Empowered to stop smoking: The impact of a SDT smoking cessation intervention on economically disadvantaged whites and blacks
Authors: Figueroa-Moseley C. D. , Williams G. C. , Morrow G. R. , Jean-Pierre P. , Carroll J. , Ryan J. 
Published: March 2020

1012 Background: Few studies have examined the potential influence of an empowering Self Determination Theory (SDT) intervention on reducing smoking behaviors and outcomes for Whites and Blacks. Objectives: To determine if empowerment to stop smoking is associated with smoking outcomes in Whites and Blacks, and to examine if empowerment to stop smoking improved under the SDT Intervention vs. Usual Care conditions. Methods: A longitudinal randomized trial study was conducted to examine the effect of a SDT and health behavior change intervention for tobacco cessation among adult smokers. Participants were randomized into the SDT Intervention or the Usual Care condition. The present study includes data from a sample of 821 Whites and 177 Blacks who completed anonymous surveys at 1, 6, and 18-months intervals on empowerment to stop smoking (Perceived Competence Scale, Treatment Self-Regulation Questionnaire), demographics, and smoking behaviors. Results: Stepwise logistic regressions showed that empowerment to stop smoking was associated with quitting smoking at 1, 6, and 18 month follow-up for both treatment conditions. At one month, participants in the SDT Intervention with the highest levels of empowerment were 6.3 times more likely to quit smoking as compared with those in the usual care condition who were only 3.15 times as likely to quit smoking. Similar findings were found at 6 months and at 18 months (6- month SDT Intervention Empowerment High: (OR = 8.66, 95% C.I. 4.6, 16.3); 6 month Usual Care Empowerment High: (OR = 3.10, 95% C.I. 1.4, 7.0); 18- month SDT Intervention Empowerment High: (OR = 4.10, 95% C.I. 2.2, 7.5); 18 month Usual Care Empowerment High: (OR = 3.11, 95% C.I. 1.3, 7.7). In the SDT Intervention at 6 months being Black increased successful quitting by 2.4 times. Conclusions: Findings indicate that at each time-point the SDT Intervention empowered more participants to stop smoking than usual care alone. Findings also suggest that Blacks may increase their ability to stop smoking in the SDT Intervention condition. These preliminary findings highlight the need to further investigate the possible roles of empowerment interventions in smoking cessation among Whites and Blacks, especially cancer patients. No significant financial relationships to disclose.
Disclosure patterns and decision making preferences in BRCA 1/2 mutation carriers with young adult and minor children
Authors: Bradbury A. R. , Daugherty C. K. , Dignam J. , Ibe C. , Auh S. , Fay H. , Cummings S. A. , White M. A. , Olopade O. I. 
Published: March 2020

1015 Background: Genetic testing of minors for adult-onset diseases has generally been discouraged. Yet, limited data suggests that many BRCA mutation carriers discuss their test results with their minor children. How parents make the decision to share this information and the effects on their health, their child and the family remains unknown. Methods: We sought to evaluate disclosure patterns and decision making practices among BRCA1/2 mutation carriers with children under the age of 25. 42 parents (with 86 children) completed a semi-structured telephone interview regarding communication of their genetic test results to their children. Chi-squared tests to assess associations between parent/child characteristics and disclosure were computed using robust variance estimates to account for clustering by family unit. Results: 55% of parents discussed hereditary risk of cancer and/or their genetic test results with at least one child. Factors associated with disclosure included older child age (p<0.001), female parent gender (p=0.049), parent history of prophylactic surgery (mastectomy: p = 0.021, oophorectomy: p<0.001) and education limited to high school (p=0.085). Child gender and parent’s history of cancer were not significantly associated with disclosure. Most participants reported themselves (45%) or their spouse (40%) as the most important person in the decision to disclose. Reports of physician (14%) and genetic counselor (21%) involvement were low. Conclusions: Parental decisions to disclose BRCA test results to children are complex and may reflect differences in perceptions of genetic disease. Further research is needed to understand parental motivations for disclosure and to define a role for health care professionals to improve counseling and recommendations regarding the risks and benefits of early communication of genetic risk to children. No significant financial relationships to disclose.
Cancer risk management practices of non-carriers within BRCA1/2 mutation positive families in the Kathleen Cunningham Consortium for Research into Familial Breast Cancer (kConFab)
Authors: Dawson S. , McKinley J. , Jenkins M. , McLachlan S. , Lindeman G. , Friedlander M. , Hopper J. , Phillips K. 
Published: March 2020

1020 Background: This study prospectively evaluated risk management practices of true BRCA1/2 negative women. Methods: A questionnaire was mailed to 471 non-carriers from mutation positive families 3 years after their enrolment in the kConFab breast cancer (BC) family cohort study. Women who had received their mutation result had pre-test counselling and result disclosure in one of 16 Family Cancer Clinics nationwide. Undertaking mammography more often than 2 yearly (Australian population guidelines), clinical breast examination (CBE) more often than yearly, breast self-examination (BSE) more often than monthly and any trans-vaginal ultrasound (TVU) or CA-125 was considered over screening. Linear logistic regression was used to identify factors (age, marital status, education, parity, ethnicity, place of residence, time since disclosure of result, family history) associated with over screening. Results: 347 women responded (74%); 260 were excluded from this analysis (self-reported not knowing their mutation status, 207; uninformative screening data due to proximity of result disclosure to questionnaire administration, 47; developed cancer, 3; pregnancy, 3), leaving 87 subjects. Mean follow up was 4.4 years. Proportions over-screening were; mammography 53%, CBE 10%, BSE 11%, TVU 10% and CA125 10%. No measured factor was associated with over-utilization of BC screening. Women with > one relative with OC were significantly more likely to over-utilize TVU (OR 8.1, CI 1.6–42 P=0.01) and CA125 (OR 19.6, CI 3.1–121 P=0.001) compared to women with ≤ one relative with OC. One woman underwent bilateral mastectomy and 1 bilateral oophorectomy; none used chemoprevention. Conclusions: A major benefit of learning one′s negative mutation status is that the intensity of risk management practices can be reduced to that appropriate for the general population. However, non-carriers with a strong family history of OC tend to inappropriately use OC screening. The reasons are unclear but need elucidation given the potential for harm. The reasons for over-utilization of mammography in 53% also warrant further study. No significant financial relationships to disclose.
Automated data base screening of a population-based cohort of stage 1 colon cancer patients for eligibility in NSABP P-3, a polyp prevention study with celecoxib at Kaiser Permanente Northern California (KPNC)
Authors: Somkin C. P. , Gross R. , Liu H. , Fehrenbacher L. 
Published: March 2020

1021 Background: Adjuvant/Prevention approaches should be designed to have broad applicability for maximum effectiveness. Celecoxib had generated interest as a polyp/colon cancer (CC) preventive agent. We used KPNC electronic data bases to identify consecutive Stage I CC patients and determine their eligibility for NSABP P-3, a polyp prevention study utilizing celecoxib in resected stage I CC. Methods: After IRB approval of both the P-3 study and use of KP data bases for recruitment, we prospectively screened all newly diagnosed CC patients within KPNC (1120 new patients a year) for stage I CC and P-3 eligibility. We identified 121 Stage I CC patients from 9/1/04 to 8/1/05 and using electronic data we screened these patients for 10-year life expectancy and other eligibility criteria. We confirmed each pathology diagnosis and stage by direct review. Results: Without chart review or patient history and exam, we found 65% of the patients were ineligible (IE) for any or multiple reasons. The average patient age was 68.9 years. 133 IE criteria were met by the 121 patients. 32% of patients were IE by age, though for only 11% was age the only criteria met. Other IE included 11% prior invasive CA, 19% coronary disease, 11% sulfa allergy, 8% coumadin usage, 7% prior CVA/TIA, 22% other GI or thrombotic criteria. It is likely that in-person history and examination would increase these IE numbers and reveal other barriers. Conclusions: Population-based automated eligibility analysis may be helpful in evaluating feasibility of chemoprevention and adjuvant trials and more importantly in determining their applicability to the whole population at risk. No significant financial relationships to disclose.
Outcome-impact of a cervical cancer (CC) screening program (SP) in a developing country
Authors: Zarba J. J. , Holgado S. , Sanchez Segura M. , Gonzalez A. , Lorente C. , Monroy C. , Cano Busnelli V. , Elias A. 
Published: March 2020

1032 Background: CC is the 2nd cause of cancer death in women in Argentine. Early detection following screening programs has demonstrated to reduce mortality in CC. The evaluation of the efficacy and efficiency of CC SP is associated with the proportion of positive cases in the smears and with the relation between pre-invasive lesion (CIN III) and invasive carcinoma (IC) in the biopsies done in positive cases. In 1997 a population based CC screening program was started in our province. The objective of this trial was to determinate the relationship between CIN III and IC in the program population and compare this results with this proportion in pre-program years an as an indicator of the quality of the program. Methods: We analyzed 2446 cervix biopsies performed in public Hospitals of Tucuman between 1985 and 2004 (archives of biopsies of the Serv. de Patología del Hosp. Centro de Salud Z. Santillán, Regional M. Belascuain and Hospital Angel C. Padilla), Since 1997 biopsies were done in patients within the SP We analyzed the proportions of pre-invasive lesions (CIN III) and invasive lesions in periods of 4 years. Results: The proportion of CIN III by periods of 4 years was: 85–88: 13%, 90–92: 20%; 93–96: 20%; 97–00 32% and 01–04 37%. The proportion of CIN III in pre-screening years was 21% and during the SP: 54%. Conclusion: These results shows an increase of CIN III over IC which could translate into a better survival. The quality control analysis of the public programs must be central in the public health policy. [Table: see text] No significant financial relationships to disclose.
Factor analysis in early detection of malignancies
Authors: Lazarev A. F. , Petrova V. D. , Sinkina T. V. , Selezneva I. A. , Terekhova S. A. 
Published: March 2020

1033 Background: The existing methods of forecasting of malignancies and forming o of increased oncological risk groups are unserviceable for practical use because of their low reliability (no more than 84%). Methods: There was elaborated an original method for forming of increased oncological risk groups with reliability of 95%. It is based on factor analysis, including the data of phenotypes and genotypes, anamnesis, laboratory testing with further computer processing. The result lies in determination of a factor number. Its quantity forms figures of oncological risk rate. The dependence of risk rate on the quantity of a factor number is ascertained on the basis of data of more than 10000 observations ( table ). The patients with risk rate more than 80–90% are subjected to complex examination according to the elaborated algorithms. In case of absence of clinical symptoms of this or that organ lesion, each-organ search is being made in order to detect malignant neoplasms in accordance with their frequency on the territory of Altai region. Results: There were examined 4775 patients who happened to be in the zone of radioactive influence of Semipalatinsk nuclear testing ground (aged 43 years - 83 years old): male - 1639, female - 3136. 191 (4.0%) cases of cancer were detected: thyroid gland cancer - 56 cases, mammary gland cancer - 23, skin cancer - 49, uterine cervix cancer - 14, stomach cancer -11, lungs cancer -11, others -27. 5 cases of cancer in situ were revealed. Specific gravity of early forms of cancer was 96.5%. Conclusion: The research proved high effectiveness of the elaborated method for increased oncological risk group formation. [Table: see text] No significant financial relationships to disclose.
Phase II study of ixabepilone in patients (pts) with taxane-resistant metastatic breast cancer (MBC): Final report
Authors: Conte P. , Thomas E. , Martin M. , Klimovsky J. , Tabernero J. 
Published: March 2020

10505 Background: Ixabepilone is the first epothilone analog in a new class of antineoplastic agents, which optimizes the properties of the naturally occurring epothilone B. The epothilones promote tumor cell death by uniquely binding to tubulin and stabilizing microtubules. Methods: This international, multicenter, open-label Phase II trial was designed to assess the activity of ixabepilone in pts with highly resistant MBC who had progressed following taxane treatment. Eligible pts were aged ≥18 years with MBC (progressed on or within 4 months of taxane therapy [or within 6 months if adjuvant taxane only]). Pts must have received a taxane as their last regimen. Pts were excluded if they had received ≥3 prior chemotherapy regimens for MBC or had ≥Grade 2 neuropathy. Ixabepilone was administered intravenously as a 3-hour infusion at a dose of 40 mg/m2 every 3 weeks. Results: Of 49 pts (median age 54 years, range 30–81), 86% of pts had received at least two prior chemotherapy regimens. 98% had received prior anthracycline treatment. 73% of pts had progressed within 1 month of their last taxane dose. 84% had visceral metastases. Pts received a median of three cycles (range 1–5) and median cumulative dose of 120 mg/m2 (range 40–498 mg/m2). The tumor response rate (number of responders [complete and partial response]/number of response-evaluable pts) was 12% (95% CI = 4.7–26.5%). All the responders (n = 6) had partial responses; five of the six had not responded to prior taxane therapy. The responders received a median of 10.5 cycles (range 5–15) and had a median duration of response of 10.4 months (95% CI = 6.3–22.0 months). In 20 pts (41%) stable disease was reported as the best overall outcome. The majority of these pts (16 of 20, 80%) received ≥4 cycles of ixabepilone therapy. The median time to progression was 2.2 months (95% CI = 1.4–3.2 months); the median survival was 7.9 months (95% CI = 6.1–14.5 months). Conclusions: Ixabepilone (40 mg/m2 as a 3-hour infusion every 3 weeks) demonstrates promising antitumor activity, along with an acceptable safety profile in pts with clearly defined taxane-resistant MBC. [Table: see text]
Final efficacy results of a phase I/II trial of ixabepilone in combination with capecitabine in patients with metastatic breast cancer (MBC) previously treated with a taxane and an anthracycline
Authors: Bunnell C. A. , Klimovsky J. , Thomas E. 
Published: March 2020

10511 Background: Ixabepilone is an epothilone B analog that has demonstrated efficacy in taxane-sensitive and taxane-resistant MBC. Differing mechanisms of action and minimally overlapping toxicities provide the potential for synergy between ixabepilone and other cytotoxics. Methods: This open-label Phase I/II study was conducted to determine the recommended Phase II (and III) doses of ixabepilone and capecitabine using a 3-hour infusion of ixabepilone given on Day 1 (Schedule A) or a 1-hour infusion of ixabepilone given for 3 consecutive days (Schedule B) in combination with capecitabine given orally on Days 1–14 every 21 days in patients (pts) with MBC previously treated with a taxane and an anthracycline in the adjuvant or metastatic setting. Pts were excluded if they had received >3 prior chemotherapy regimens in the metastatic setting. Tumor response was determined after every 2 cycles. Results from the 62 patients treated with ixabepilone 40 mg/m2 as a 3 hr-infusion and capecitabine 2000 mg/m2 are shown here. Results: 56/62 patients (90%) were aged <65 yrs. 80% of pts had visceral disease and 44% were ER/PR/HER-2 negative. 44% of pts had received ≥2 prior chemotherapies in the metastatic setting. Pts received a median of 4 cycles (range 1–20). The overall response rate was 30% (15/50; 95% CI = 17.9–44.6%) comprised of one (2%) complete response and 14 (28%) partial responses. All 15 of the responders had extensive tumor metastases at baseline. Four of the 15 responders were triple negative for ER/PR/HER-2. The median time to response was 6 weeks (range 5–14 weeks), with most responders achieving an objective response by the end of Cycle 2. The median duration of response was 6.9 months (95% CI = 4.3–9.7 months). Conclusions: The recommended Phase II (and III) doses were 40 mg/m2 ixabepilone (3-hour infusion on Day 1 every 21 days) and 2000 mg/m2 capecitabine (2 doses on Days 1–14 every 21 days). This ixabepilone/capecitabine combination demonstrated promising synergistic antitumor activity and a manageable safety profile in pts with MBC previously treated with a taxane and an anthracycline. [Table: see text]