bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunohistochemistry Versus Microsatellite Instability Testing in Phenotyping Colorectal Tumors
Authors: Lindor Noralane M. , Burgart Lawrence J. , Leontovich Olga , Goldberg Richard M. , Cunningham Julie M. , Sargent Daniel J. , Walsh-Vockley Catherine , Petersen Gloria M. , Walsh Michael D. , Leggett Barbara A. , Young Joanne P. , Barker Melissa A. , Jass Jeremy R. , Hopper John , Gallinger Steve , Bapat Bharati , Redston Mark , Thibodeau Stephen N. 
Published: February 2017

PURPOSE: To compare microsatellite instability (MSI) testing with immunohistochemical (IHC) detection of hMLH1 and hMSH2 in colorectal cancer. PATIENTS AND METHODS: Colorectal cancers from 1,144 patients were assessed for DNA mismatch repair deficiency by two methods: MSI testing and IHC detection of hMLH1 and hMSH2 gene products. High-frequency MSI (MSI-H) was defined as more than 30% instability of at least five markers; low-level MSI (MSI-L) was defined as 1% to 29% of loci unstable. RESULTS: Of 1,144 tumors tested, 818 showed intact expression of hMLH1 and hMSH2. Of these, 680 were microsatellite stable (MSS), 27 were MSI-H, and 111 were MSI-L. In all, 228 tumors showed absence of hMLH1 expression and 98 showed absence of hMSH2 expression: all were MSI-H. CONCLUSION: IHC in colorectal tumors for protein products hMLH1 and hMSH2 provides a rapid, cost-effective, sensitive (92.3%), and extremely specific (100%) method for screening for DNA mismatch repair defects. The predictive value of normal IHC for an MSS/MSI-L phenotype was 96.7%, and the predictive value of abnormal IHC was 100% for an MSI-H phenotype. Testing strategies must take into account acceptability of missing some cases of MSI-H tumors if only IHC is performed.
Role of Health-Related Quality of Life in Palliative Chemotherapy Treatment Decisions
Authors: Detmar S. B. , Muller M. J. , Schornagel J. H. , Wever L. D.V. , Aaronson N. K. 
Published: February 2017

PURPOSE: To determine the frequency with which health-related quality-of-life (HRQL) considerations lead to modification or discontinuation of palliative chemotherapy, and the association between physicians’ ratings of patients’ HRQL and such treatment decisions. METHODS: Four consecutive medical consultations of 203 patients receiving outpatient palliative chemotherapy were tape-recorded and the content was analyzed to determine the frequency of and reasons for treatment alterations. Physicians rated their patients’ HRQL by using the COOP/WONCA health assessment charts. Data on tumor response and treatment toxicity were obtained from the audiotapes and, when necessary, were confirmed by medical chart audits. RESULTS: Treatment was modified in 54 cases (26%) and discontinued in 40 (20%). The primary reasons for modifying treatment were toxicity (n = 22), HRQL considerations (n = 18), and tumor progression (n = 14). The primary reasons for discontinuation of treatment were tumor progression (n = 23), HRQL considerations (n = 6), and toxicity (n = 3). For eight patients, a combination of tumor progression and HRQL issues resulted in discontinuation of treatment. Treatment decisions were associated significantly with physicians’ global ratings of patients’ HRQL but not with more specific HRQL domains. In the presence of tumor progression or serious toxicity, HRQL considerations played little or no role in treatment decisions. Furthermore, approximately 70% of patients without evidence of tumor progression or toxicity, but with seriously impaired HRQL, continued to receive their treatment as planned. CONCLUSION: Contrary to previous findings based on physicians’ self-report data, HRQL considerations seem to play a relatively minor role in decisions regarding modification or discontinuation of palliative chemotherapy.
Novel Artificial Neural Network for Early Detection of Prostate Cancer
Authors: Djavan Bob , Remzi Mesut , Zlotta Alexandre , Seitz Christian , Snow Peter , Marberger Michael 
Published: February 2017

PURPOSE: Two artificial neural networks (ANN) for the early detection of prostate cancer in men with total prostate-specific antigen (PSA) levels from 2.5 to 4 ng/mL and from 4 to 10 ng/mL were prospectively developed. The predictive accuracy of the ANN was compared with that obtained by use of conventional statistical analysis of standard PSA parameters. PATIENTS AND METHODS: Consecutive men with a serum total PSA level between 4 and 10 ng/mL (n = 974) and between 2.5 and 4 ng/mL (n = 272) were analyzed. A separate ANN model was developed for each group of patients. Analyses were performed to determine the presence of prostate cancer. RESULTS: The area under the receiver operator characteristic (ROC) curve (AUC) was 87.6% and 91.3% for the 2.5 to 4 ng/mL and 4 to 10 ng/mL ANN models, respectively. For the latter model, the AUC generated by the ANN was significantly higher than that produced by the single variables of total PSA, percentage of free PSA, PSA density of the transition zone (TZ), and TZ volume (P < .01), but not significantly higher compared with multivariate analysis. For the 2.5 to 4 ng/mL model, the AUC of the ANN ROC curve was significantly higher than the AUCs for percentage of free PSA (P = .0239), PSA-TZ (P = .0204), and PSA density and total prostate volume (P < .01 for both). CONCLUSION: The predictive accuracy of the ANN was superior to that of conventional PSA parameters. ANN models might change the way patients referred for early prostate cancer detection are counseled regarding the need for prostate biopsy.
Age, Sex, and Racial Differences in the Use of Standard Adjuvant Therapy for Colorectal Cancer
Authors: Potosky Arnold L. , Harlan Linda C. , Kaplan Richard S. , Johnson Karen A. , Lynch Charles F. 
Published: February 2017

PURPOSE: Dissemination of efficacious adjuvant therapies for resectable colorectal cancer has not been comprehensively described. Trends, patterns, and outcomes of adjuvant therapy for colorectal cancer, focusing on age, sex, and racial/ethnic differences, are reported. MATERIALS AND METHODS: Population-based random samples of patients diagnosed with colorectal cancer diagnosed in nine geographic areas were collected annually between 1987 and 1991 and in 1995 (n = 4,706). Data were obtained from medical record reviews. Multiple logistic regression was used to assess the use of standard adjuvant chemotherapy for colon and rectal cancers. The Cox proportional hazards model was used to assess 9-year mortality. RESULTS: From 1987 until 1995, the use of adjuvant therapy increased in all age groups. There was an increase starting in 1989 for colon and in 1988 for rectal cancer. Use of standard therapy was 78% for those younger than 55 years and 24% for those older than 80 years. White patients received standard therapy more frequently than African-Americans (odds ratio, 1.75; 95% confidence interval [CI], 1.09 to 2.83). All-cause and cancer-specific mortality exceeding 9 years were lower in those who received standard therapy (all-cause risk ratio [RR], 0.73; 95% CI, 0.61 to 0.88; cancer-specific RR, 0.87; 95% CI, 0.70 to 1.09). CONCLUSION: Standard adjuvant therapies for colorectal cancer disseminated into community practices during the 1990s. However, evidence exists of differential use of therapies by older patients and by African-Americans. The use of standard therapies in the general population is associated with lower mortality. Improved dissemination of standard adjuvant therapies to all segments of the population could help reduce mortality.
Marginal Decrease in Mortality and Marked Increase in Incidence as a Result of Neuroblastoma Screening at 6 Months of Age: Cohort Study in Seven Prefectures in Japan
Authors: Yamamoto Keiko , Ohta Shigeru , Ito Etsuro , Hayashi Yutaka , Asami Tadashi , Mabuchi Osamu , Higashigawa Masamune , Tanimura Masako 
Published: February 2017

PURPOSE: To determine the usefulness of 6-month screening for neuroblastoma. PATIENTS AND METHODS: The cumulative incidence rates (IRs) and cumulative mortality rates (MRs) of neuroblastoma in children younger than 60 months of age were analyzed for control (n = 713,025), qualitative screening (Qual Screen, n = 1,142,519), and quantitative screening (Quan Screen, n = 550,331) cohorts, and for Screened and Unscreened subgroups within screening cohorts. RESULTS: IRs (per 100,000) for infants aged 6 to 11 months were 1.12 in Control, 5.69 in Qual Screen (P < .0001), and 17.81 in Quan Screen (P < .0001); IRs for children aged 12 to 59 months were 7.29 in Control, 5.86 in Qual Screen (P = .28), and 6.36 in Quan Screen (P = .60). IRs for children aged 12 to 59 months in Unscreened or Screened subgroups remained at the same level. When patients diagnosed at younger than 6 months of age were excluded, the MR (per 100,000) under 60 months for Control was 4.21; those in Unscreened and Screened subgroups were 3.84 and 2.53 in Qual Screen (P = .30), and 3.20 and 1.97 in Quan Screen (P = .73), respectively; MRs between Control and Unscreened subgroups revealed no significant differences (P = .89 in Qual Screen, P = .85 in Quan Screen). CONCLUSION: Six-month screening resulted in a marked increase in incidence for infants with no significant decrease in incidence for children older than 1 year of age. A decrease in mortality was observed, but it was not significant. The usefulness of screening is questionable, because the decrease of mortality should be balanced against the adverse effect of overdiagnosis and the psychological burden on parents and children.
Incidence and Prognostic Significance of Complete Axillary Downstaging After Primary Chemotherapy in Breast Cancer Patients With T1 to T3 Tumors and Cytologically Proven Axillary Metastatic Lymph Nodes
Authors: Rouzier Roman , Extra Jean-Marc , Klijanienko Jerzy , Falcou Marie-Christine , Asselain Bernard , Vincent-Salomon Anne , Vielh Philippe , Bourstyn Edwige 
Published: February 2017

PURPOSE: To determine the incidence and prognostic significance of eradication of cytologically proven axillary lymph node metastases in breast cancer patients treated with primary chemotherapy. PATIENTS AND METHODS: Between January 1985 and December 1994, 152 breast cancer patients with invasive T1 to T3 tumors and axillary metastases cytologically proven by fine-needle sampling underwent primary chemotherapy followed by lumpectomy or mastectomy, level I and II axillary lymph node dissection, and irradiation. We studied pathologic complete responses (pCRs) of axillary nodes and breast tumors, as well as predictors of distant metastases. RESULTS: Thirty-five patients (23%) had axillary pCRs, and 20 patients (13.2%) had pCRs of primary breast tumors. Scarff-Bloom-Richardson grade 3 tumors (P = .04) and a clinical response to chemotherapy ≥ 50% (P = .003) were associated with negative axillary status at dissection. An initial tumor size ≤ 3 cm (63 patients) was associated with pCR of the primary tumor (P = .02) but not with complete histologic clearance of axillary lymph nodes. The median length of follow-up was 75 months. In the univariate analysis, age greater than 40 years (P = .003), absence of residual nodal disease (P = .01), and pCR of the tumor (P = .05) were associated with better distant disease-free survival. Five-year distant disease-free survival rates were 73.5% ± 14.9% among patients with no involved nodes at the time of surgery and 48.7% ± 9.2% among patients with residual nodal disease. In the multivariate Cox regression analysis, parameters associated with poor distant disease-free survival were age ≤ 40 years (P = .002), persistence of nodal involvement (P = .03), and S-phase fraction greater than 4% (P = .02). CONCLUSION: Our results suggest that axillary status is a better prognostic factor than response of the primary tumor to primary chemotherapy.
Standardized Uptake Value of 2-[18F] Fluoro-2-Deoxy-d-Glucose in Predicting Outcome in Head and Neck Carcinomas Treated by Radiotherapy With or Without Chemotherapy
Authors: Allal Abdelkarim S. , Dulguerov Pavel , Allaoua Mohamed , Haenggeli Charles-André , El Ghazi El Abbes , Lehmann Willy , Slosman Daniel O. 
Published: February 2017

PURPOSE: In patients with head and neck cancer enrolled onto a prospective study of positron emission tomography (PET), pretreatment 2-[18F] fluoro-2- deoxy-d-glucose (FDG) uptake was evaluated as a predictor of local control and disease-free survival (DFS) after treatment by radiotherapy (RT) with or without chemotherapy. PATIENTS AND METHODS: We studied 63 patients with carcinomas of the head and neck who had an FDG-PET scan before radical RT. Tumor FDG uptake was measured with the semiquantitative standardized uptake value (SUV). All patients but one were treated with accelerated or hyperfractionated RT schedules. Thirteen patients received concomitant cisplatin-based chemotherapy. RESULTS: In 25 patients who presented with any component of treatment failure, the SUV was significantly higher than in the remaining patients without any such failure. Patients having tumors with high FDG uptake had a significantly lower 3-year local control (55% v 86%, P = .01) and DFS (42% v 79%, P = .005) compared with patients having low uptake tumors. In the multivariate analysis, the only factor that retained its significance for DFS was SUV category, whereas T category was of borderline significance. For local control, T category remained a significant factor, whereas a lower local control was observed for tumors with a high SUV compared with those with low SUV. CONCLUSION: FDG uptake, as measured by the SUV, has potential value in predicting local control and DFS in head and neck carcinomas treated by RT. High FDG uptake may be a useful parameter for identifying patients requiring more aggressive treatment approaches.
Elevated Serum HER-2/neu Level Predicts Decreased Response to Hormone Therapy in Metastatic Breast Cancer
Authors: Lipton Allan , Ali S.M. , Leitzel K. , Demers L. , Chinchilli V. , Engle L. , Harvey Harold A. , Brady C. , Nalin C.M. , Dugan M. , Carney W. , Allard J. 
Published: February 2017

PURPOSE: To determine the effect of elevation of serum HER-2/neu on response to hormone therapy. PATIENTS AND METHODS: Seven hundred nineteen metastatic patients with estrogen receptor–positive (ER+), progesterone receptor–positive, or both or ER status unknown breast cancer were randomized in three independent clinical trials to receive second-line hormone therapy with either megestrol acetate or an aromatase inhibitor (fadrozole or letrozole). An automated enzyme-linked immunosorbent assay specific for the extracellular domain of the HER-2/neu (c-erbB-2) oncoprotein product was used to detect serum levels. RESULTS: Two hundred nineteen patients (30%) had elevated serum HER-2/neu protein levels, using the mean + 2 SD (15 ng/mL) from the serum of healthy women as an upper limit. Response to treatment was available for 711 patients. The response rate (complete responses plus partial responses plus stable disease) to endocrine therapy was 45% in 494 patients with nonelevated and 23% in 217 patients with elevated serum HER-2/neu levels (P < .0001). Median duration of treatment response (using the time to progression [TTP] variable for patients who responded) was shorter in the group with elevated serum HER-2/neu levels (11.7 months) compared with the patient group with nonelevated levels (17.4 months). TTP, time to treatment failure, and median survival (17.2 months v 29.6 months) were also significantly shorter in the patients with elevated serum HER-2/neu levels (P < .0001). CONCLUSION: Patients with ER+ and serum HER-2/neu-positive metastatic breast cancer are less likely to respond to hormone treatment and have a shorter duration of response than ER+ and serum HER-2/neu–negative patients. Their survival duration is also shorter.
Clinical Characteristics of Individuals With Germline Mutations in BRCA1 and BRCA2: Analysis of 10,000 Individuals
Authors: Frank Thomas S. , Deffenbaugh Amie M. , Reid Julia E. , Hulick Mark , Ward Brian E. , Lingenfelter Beth , Gumpper Kathi L. , Scholl Thomas , Tavtigian Sean V. , Pruss Dmitry R. , Critchfield Gregory C. 
Published: February 2017

PURPOSE: To assess the characteristics that correlate best with the presence of mutations in BRCA1 and BRCA2 in individuals tested in a clinical setting. PATIENTS AND METHODS: The results of 10,000 consecutive gene sequence analyses performed to identify mutations anywhere in the BRCA1 and BRCA2 genes (7,461 analyses) or for three specific Ashkenazi Jewish founder mutations (2,539 analyses) were correlated with personal and family history of cancer, ancestry, invasive versus noninvasive breast neoplasia, and sex. RESULTS: Mutations were identified in 1,720 (17.2%) of the 10,000 individuals tested, including 968 (20%) of 4,843 women with breast cancer and 281 (34%) of 824 with ovarian cancer, and the prevalence of mutations was correlated with specific features of the personal and family histories of the individuals tested. Mutations were as prevalent in high-risk women of African (25 [19%] of 133) and other non-Ashkenazi ancestries as those of European ancestry (712 [16%] of 4379) and were significantly less prevalent in women diagnosed before 50 years of age with ductal carcinoma in situ than with invasive breast cancer (13% v 24%, P = .0007). Of the 74 mutations identified in individuals of Ashkenazi ancestry through full sequence analysis of both BRCA1 and BRCA2, 16 (21.6%) were nonfounder mutations, including seven in BRCA1 and nine in BRCA2. Twenty-one (28%) of 76 men with breast cancer carried mutations, of which more than one third occurred in BRCA1. CONCLUSION: Specific features of personal and family history can be used to assess the likelihood of identifying a mutation in BRCA1 or BRCA2 in individuals tested in a clinical setting.
Women Experience Greater Toxicity With Fluorouracil-Based Chemotherapy for Colorectal Cancer
Authors: Sloan Jeff A. , Goldberg Richard M. , Sargent Daniel J. , Vargas-Chanes Delfino , Nair Suresh , Cha Steven S. , Novotny Paul J. , Poon Michael A. , O’Connell Michael J. , Loprinzi Charles L. 
Published: February 2017

PURPOSE: The toxicity profile of fluorouracil (5-FU)–based chemotherapy given on 5 consecutive days at doses of 370 to 450 mg/m2 has been well documented. A meta-analysis of six North Central Cancer Treatment Group (NCCTG) cancer control trials involving 786 patients indicated that women treated with this type of regimen experienced more severe stomatitis and leukopenia than men. After these findings, an additional meta-analysis of the toxicity profiles on five NCCTG colorectal cancer treatment trials was undertaken. METHODS: Data for 1,093 women and 1,355 men from 12 different treatment arms were included. The primary end points were the incidence of stomatitis, leukopenia, alopecia, diarrhea, nausea, and vomiting, recorded with standard National Cancer Institute common toxicity criteria. Fisher’s exact test was used to compare incidence and severity across sexes, supplemented by Forrest meta-analysis plots and logistic regression. RESULTS: The incidence of four out of six toxicities studied was significantly greater for women than men; the exceptions were severe nausea and vomiting. Overall, almost half of the women compared with a third of the men experienced severe toxicity (P < .0001). Logistic regression confirmed the univariate findings while adjusting for the effects of study, dose, body mass index, and age. The differences were consistent across treatment cycles. Response rates and survival distributions were the same for both sexes. CONCLUSION: This study confirms an earlier finding that women receiving 5-FU–based chemotherapy in a 5-day bolus schedule experience toxicity more frequently and with more severity than men. These data raise the question of whether the recommended initial dose of 5-FU–based chemotherapy for women should be lower than that for men.
Time Spent in Hospital in the Last Six Months of Life in Patients Who Died of Cancer in Ontario
Authors: Huang J. , Boyd C. , Tyldesley S. , Zhang-Salomons J. , Groome P. A. , Mackillop W. J. 
Published: February 2017

PURPOSE: To describe hospital bed utilization in the final 6 months of life in patients dying of cancer in Ontario, Canada. PATIENTS AND METHODS: Hospital separation records were linked to a population-based cancer registry to identify factors associated with hospitalization in the 203,713 patients who died of cancer in Ontario between 1986 and 1998. RESULTS: Between 1986 and 1998, 5.3% of all acute care beds in Ontario were devoted to the care of cancer patients in the last 6 months of life. The mean time spent in hospital in the last 6 months of life decreased from 34.3 days in 1986 to 22.7 days in 1998. Hospitalization rates increased exponentially during the last month of life. Patients younger than 50 years of age, women, and residents of poorer communities spent significantly longer in hospital than others. Hospitalization rates differed very little among the common solid tumors, but patients with CNS malignancies, the lymphomas, and the leukemias spent significantly longer in hospital than the other groups. There was significant interregional variations in hospitalization that were not explained by differences in case mix. There was a statistically significant inverse correlation between the rate of use of palliative radiotherapy and the hospital bed use in the county in which the patient resided. CONCLUSION: The total time spent in hospital in the last 6 months of life has decreased over the last decade, but acute care hospitals continue to play a large role in the care of patients who are dying of cancer.
Predictors of Smoking Initiation and Cessation Among Childhood Cancer Survivors: A Report From the Childhood Cancer Survivor Study
Authors: Emmons Karen , Li Frederick P. , Whitton John , Mertens Ann C. , Hutchinson Raymond , Diller Lisa , Robison Leslie L. 
Published: February 2017

PURPOSE: To examine the determinants of smoking behavior among participants in the Childhood Cancer Survivors Study (CCSS). METHODS: This retrospective cohort survey study was conducted among 9,709 childhood cancer survivors. Main outcomes included smoking initiation and cessation. RESULTS: Twenty-eight percent of patients reported ever smoking and 17% reported being current smokers. Standardized to United States population rates, the observed to expected (O/E) ratios and corresponding 95% confidence limits (95% CL) of cigarette smoking were 0.72 (95% CL, 0.69, 0.75) among all survivors and 0.71 (95% CL, 0.68 to 0.74) and 0.81 (95% CL, 0.70, 0.93) among whites and nonwhites, respectively. Significantly lower O/E ratios were present among both males (O/E, 0.73) and females (O/E, 0.70). Factors independently associated with a statistically significant relative risk of smoking initiation included older age at cancer diagnosis, lower household income, less education, not having had pulmonary-related cancer treatment, and not having had brain radiation. Blacks were less likely to start smoking. Survivors who smoked were significantly more likely to quit (O/E, 1.22; 95% CL, 1.15, 1.30). Among ever-smokers, factors associated with the likelihood of being a current smoker included age less than 13 years at smoking initiation, less education, and having had brain radiation; those age less than 3 years at cancer diagnosis were significantly more likely to be ex-smokers. CONCLUSIONS: Although survivors in the CCSS cohort seem to be smoking at rates below the general population, interventions are needed to prevent smoking initiation and promote cessation in this distinct population.