bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcome of patients with non-metastatic versus metastatic hormone refractory prostate cancer (HRPC) treated with second-line hormonal therapy consisting of ketoconazole (keto) plus granulocyte macrophage colony stimulating factor (GM-CSF)
Authors: Ryan C. J. , Rosenberg J. , Lin A. , Ruttner L. , Weinberg V. , Small E. 
Published: March 2020

4626 Background: Second line hormonal manipulations are frequently used in pts with HRPC. It is unknown if these manipulations are more effective in patients without clinical metastases. The efficacy of a second-line hormonal manipulation (keto plus GM-CSF) was prospectively evaluated in a cohort of HRPC patients with and without metastases. Methods: Eligible pts had progressive HRPC by consensus criteria, no prior immunotherapy, chemotherapy or keto. Pts received keto 400 mg po tid and hydrocortisone 20 mg po qAM and 10 mg po qPM. GM-CSF 250 mcg/m2 was administered SQ on days 15–28 of each 28-day cycle. Results: Forty-two of 48 planned pts have been enrolled, 30 with clinical metastases, 12 with PSA-only disease and are evaluable for PSA response, using consensus criteria. The median age is 68 years (range: 53–84), and median PSA 23.1 ng/mL (range: 5.4–306.5). The median treatment duration is 5.1 months (range: 0.3–22+). Overall, 30 of 43 patients (69%) have experienced a ≥ 50% reduction in PSA. The PSA response proportion in the non-metastatic patients is 8/12 (66%) while the response proportion in those with metastases is 16/30 (53%, chi squared p = 0.41). Twenty-three patients have discontinued therapy after a median of three cycles. Progressive disease has occurred in 17 patients, 3 of 12 patients with non-metastatic disease and in 14 of 30 patients with metastatic disease (25% vs. 47%, chi squared p=0.20). Six patients have discontinued due to toxicity or patient choice. The primary endpoint of the study, overall time to progression, has not been reached at a median follow up of 7 months. Conclusions: There was no significant difference in response proportion and progressive disease rate in HRPC patients with and without metastatic disease treated with keto/GM-CSF. While these data require prospective confirmation in a larger group of patients, they suggest that secondary hormonal manipulations are warranted in either patient group. No significant financial relationships to disclose.
Mutational profiling of protein kinases in prostate carcinoma
Authors: Andea A. , Osman I. , Scardino P. , Scher H. , Gerald W. 
Published: March 2020

4636 Background: Protein kinases are important signal transduction mediators that play a critical role in malignant transformation. However, their involvement in prostate carcinogenesis has not been fully elucidated. Methods: In this pilot study, we sequenced the coding and exon-flanking intronic regions of selected protein kinases in 15 human prostate carcinoma specimens and 2 prostate cancer cell lines using standard techniques (Agencourt Biosciences). The 15 protein kinases genes included: tyrosine kinases (EGFR, EPHA3, EPHB2, ERBB2, FES, FGFR2, KDR, KIT, MET, NTRK1, NTRK2, NTRK3), tyrosine kinase-like (BRAF), serine/threonine kinase (AKT2), and the lipid kinase (PIK3CA). We also sequenced PTEN, p53 and AR because of their known association with prostate cancer and interactions with protein kinases. Results: We identified 452 different sites of single nucleotide sequence alterations and 50 insertion/deletion changes in multiple genes in the 17 specimens. The majority were intronic or involved untranslated regions (364 single nucleotide and all indels), and therefore were not further evaluated. Of the remaining 88 coding region alterations, 59 were synonymous and 10 were previously identified single nucleotide polymorphisms leaving 19 non-synonymous coding region changes (12 in 12 patient tumors and 9 in cell lines). Sequencing of corresponding non-neoplastic tissue revealed that 4 genes with sequence alterations were also altered in the germ-line and likely represent polymorphisms (EPHA3, KDR, NTRK1 and NTRK3). Six tumor specific mutation sites have been confirmed (one mutation is yet to be studied). Three represent unreported sites of mutation in prostate cancer involving MET (1 site) and EPHB2 (2 sites) and the others involved known sites within AR (1 site) and TP53 (2 sites). Conclusions: Our study successfully identified specific mutations of tyrosine kinases occurring in prostate cancer. Evaluation of a larger sample representing natural and treated history of prostate cancer to determine frequency and clinical associations, as well as functional studies to determine the biological significance of these mutations, is needed. No significant financial relationships to disclose.
A modified CA-125 progression criterion in ovarian cancer (OC) patients (pts) receiving maintenance treatment following complete clinical response (cCR) to primary therapy
Authors: Liu P. , Moon J. , Alberts D. S. , Monk B. J. , Brady M. , Markman M. 
Published: March 2020

5080 Background: CA-125 progression criterion for OC by Vergote et al (JNCI 2000; 92:1534) has been widely adopted, with 35 U/ml as the most commonly used normal limit. Based on recent findings (ASCO Proceedings 2005, #5013), primary therapy cCR OC pts with nadir CA-125 ≤10 versus >10–20 versus >20–35 have different prognosis. We propose to modify the CA-125 progression criterion in this setting as follows: for pts with nadir ≤10, value ≥20 that is confirmed equals progression; for pts with nadir >10, value ≥ 2×nadir that is confirmed equals progression. This new criterion essentially treats 10 U/ml as the normal limit. Methods: The proposed criterion combined with RECIST was tested on SWOG 9701/GOG 178 pts (n = 287) and compared to the existing criterion. All pts achieved cCR from primary therapy and entered the above maintenance trial with CA125 ≤35. Results: Of 91 pts last known to be progression-free by existing criterion, 10 (11%) new progressions were called. Available CA-125 values continued to rise in all except 1 case (1%). For 196 pts with known progressive disease, the progression date was unchanged by the new criterion in 42%, and was earlier by ≤60 days in 31%, 61–180 days in 16% and >180 days in 11% (overall median days early = 56). Conclusions: In a series of 39 primary therapy cCR pts with CA-125 ≤35, Santillan et al found a progressive low-level increase in CA-125 to be strongly predictive of disease recurrence (JCO 2005; 23:9338). Similarly, initial testing of the proposed CA-125 criterion demonstrated a low false positive rate and early detection of disease progression >2 months in approximately 30% of the same first line complete responders with progressive disease during or after maintenance treatment. Such pts can potentially benefit from starting alternative treatments early. The proposed criterion should be further investigated. No significant financial relationships to disclose.
Concommitant boost: An effective regimen in locoregionally advanced head and neck cancers—A phase III randomised trial from a single institute in India
Authors: Sastri G. J. , Ghoshal S. , Kehwar T. S. , Sharma S. C. 
Published: March 2020

5546 Background: The basic objective of this randomized trial was to test the efficacy of concomitant boost against standard fractionation in advanced head and neck cancers. Material and Methods: 285 patients with advanced head and neck cancers were randomized to receive either conventional radiotherapy 66 Gy/33 #/6.5 weeks or concomitant boost to a dose of 67.5 Gy/40 #/5 weeks. Results: The compliance to treatment was equal in both the arms.With a median follow up of 24 months, patients treated with concomitant boost had a significantly better two-year disease free survival and overall survival (p = 0.007 and p = 0.001respectively) than those treated by conventional fractionation. Grade III mucositis was seen in 35% patients in the concomitant boost arm and 19% in the conventional arm. On univariate analysis, the difference in outcome of oropharyngeal lesion p = 0.000, T3&T4 lesions (p = 0.004), Stage IV disease (p = 0.0005) and N+ disease (p = 0.000) were statistically significant in favour of concomitant boost arm. On multivariate analysis base of tongue site was an independent prognostic factor. Conclusions: Concomitant boost is an effective regimen in advanced head and neck cancers. In developing countries where 50–60% patients present at an advanced stage, this seems to be an optimal radiation therapy regimen especially in advanced oropharyngeal cancers. No significant financial relationships to disclose.
Cancer patients’ attitudes toward future research uses of their donated tissue: Preliminary results of a mail survey study
Authors: Helft P. R. , Eckles R. E. , Kempf J. , Johnson-Calley C. S. , Brooks J. , Meslin E. M. 
Published: March 2020

6009 Background: Millions of tissue samples are stored in the United States, but little is known about the attitudes of tissue donors. Understanding the attitudes of those who donate tissue for use in future research would inform the design of studies using stored tissues (ST). Methods: Eligible subjects included cancer patients who donated remaining tissue after biopsy or surgery to the Indiana University Cancer Center Tissue Bank. All subjects signed informed consent to donate tissue. A convenience sample were approached for participation. A survey instrument was developed from literature review and expert input, and refined by focus groups. Results: 243 surveys were mailed, and 196 completed surveys were returned (response rate 80.7%). Respondents were 70% married, 93% white, 54% female. 57% had completed at least some college. Average age was 60. Average time since diagnosis was 13.8 months. 81% of respondents remembered donating tissue. 61% were not at all or a little concerned about the privacy of their ST. >80% of subjects agreed that their ST could be used in future research on their type of cancer, other cancers, and other diseases,. Non-whites were less likely than whites to allow tissue to be used in research (p = 0.0128). Around 40% of respondents agreed that researchers should have to recontact them before using their ST. Non-whites and less educated subjects were more likely to want to be recontacted for each research use of their ST. 90% of subjects would allow their ST to be used by university researchers, but only 60% agreed that ST could be used by pharmaceutical companies. 39% objected to the use of STs to develop a treatment for profit. No differences were found in willingness of ST to be used in future research whether samples were identified, de-identified, or linked. 60% of respondents wanted to be notified of research results that would impact their, or their children’s, health whether treatments were available or not, and whether results had been validated or not. Conclusions: This cohort of cancer patients was very willing to allow their ST to be used in future research on all conditions, but a significant minority desired to be recontacted each time ST were used. These findings do not support policies based on a simple presumed consent model. No significant financial relationships to disclose.
Correlates of patient referral to surgeons for treatment of breast cancer
Authors: Katz S. J. , Hofer T. P. , Hawley S. , Lantz P. M. , Janz N. K. , Schwartz K. , Liu L. , Deapen D. , Morrow M. 
Published: March 2020

6032 Background: Characteristics of surgeons and their practice settings have been associated with cancer treatments and outcomes. Yet, there is little information about factors that are associated with referral pathways to surgeons and treatment settings. Methods: We merged and analyzed tumor registry and survey data from all women with DCIS and a 20% random sample of women with invasive breast cancer diagnosed in 2002 and reported to the Detroit and Los Angeles SEER registries (N = 1,844, response rate 77.4%,) and their surgeons (N = 365, response rate 80.0%). Results: About half of the patients (54.2%) reported that they were referred to their surgeon by another provider or health plan; 20.3% reported that they selected their surgeon; 21.9% reported that they both were referred and were involved in selecting their surgeon; and the remaining patients (4.9%) reported that they had a prior relationship with their surgeon primarily through previous surgery. Selecting their surgeon based on reputation was more frequently reported by white patients (36.5% vs 26.5%, p < .001), and more highly educated patients (40.0% and 21.6%, respectively for highest and lowest education categories, p < .001). Patients who selected their surgeon based on reputation were more likely to have received treatment from a high volume surgeon (adjusted odds ratio 2.3; 95% CI 1.7, 3.2) and more likely to have been treated in an American College of Surgeon approved cancer program or NCI-designated cancer center (adjusted odds ratio 1.8; 95% CI 1.1, 2.8; 3.0 95% CI 1.6, 5.3, respectively). Patients who were referred to their surgeon were less likely to be treated in an NCI-designated cancer center (adjusted OR 0.4; 95% CI 0.2, 0.8). Conclusions: Women with breast cancer who actively participate in the surgeon selection process are more likely to be treated by more experienced surgeons and in hospitals with approved cancer programs. Patients should be aware that provider or health plan-based referral may not connect them with the most experienced surgeon or comprehensive practice setting in their community. An active patient role in the surgeon selection process has important implications for both the type of treatment received and where care is delivered. No significant financial relationships to disclose.
Economic evaluation of DVd versus VAd in the treatment of multiple myeloma: Results from a phase III multicenter randomized clinical trial
Authors: Rifkin R. M. , Hussein M. , Iskandar R. , O’Sullivan A. , Thompson D. , Forlenza J. , Fruchtman S. , Wildgust M. , McGarry L. 
Published: March 2020

6050 Background: A randomized Phase III clinical trial of pegylated liposomal doxorubicin, vincristine, and reduced-dose dexamethasone (DVd) versus conventional doxorubicin, vincristine, and reduced-dose dexamethasone (VAd) found similar efficacy in the treatment of newly-diagnosed multiple myeloma (Cancer, in press). However, observed clinical advantages of DVd included less toxicity and supportive care. (Cancer In press). Methods: This economic evaluation was conducted as a piggyback to the clinical trial. Utilization data were collected prospectively for enrolled patients (DVd = 97; VAd = 95). Costs were estimated by applying standard US unit costs in 2004 to observed utilization. We compared resource utilization and costs for study drug administration, other care (hospitalizations due to AEs, tests, transfusions, and concomitant medications), and total costs during follow-up for patients receiving DVd versus VAd using 2-sided t-tests. Results: DVd patients required significantly fewer hospital (1.5 vs 8.5; p < 0.01) and clinic days (4.8 vs 14.4; p < 0.01) for study drug administration. Costs of study drug were significantly higher for DVd patients ($16,181 vs $788; p < 0.01), but lower hospitalization costs ($3,311 vs $18,492; p < 0.01) and clinic costs ($797 vs $2,412; p < 0.01) for drug administration more than offset these costs, resulting in nominally lower overall study drug administration costs for DVd versus VAd ($20,289 vs $21,692; p = 0.64). No other component of care differed significantly between the two groups (costs of other care: $14,152 for DVd vs $14,154 for VAd; p = 0.99) and overall treatment costs ($34,442 for DVd vs $35,846 for VAd; p = 0.76) were similar in the two groups. DVd patients had approximately 10 additional days of follow-up over the trial period (149.4 vs 139.2) versus VAd patients. Conclusions: Despite higher drug acquisition costs, use of DVd did not increase the overall cost of treatment compared to VAd. [Table: see text]
Cost-effectiveness of influenza vaccination of adult cancer patients
Authors: Avritscher E. B. , Cooksley C. D. , Geraci J. M. , Bekele B. N. , Cantor S. B. , Rolston K. V. , Elting L. S. 
Published: March 2020

6079 Background: Despite recommendations to immunize all patients at increased risk from underlying immunosuppressive disease against influenza, many insurance plans do not cover the vaccine. We analyzed the cost-effectiveness of vaccinating adult cancer patients against influenza from the perspective of a third-party payer. Methods: We developed a decision-analytic model using epidemiological, vaccine effectiveness, resource utilization, cost, and utility data from published sources, supplemented with data collected from our institutional accounting system. Two strategies were compared: vaccination of adult cancer patients against influenza, and no vaccination. The cost-effectiveness analysis included charges (inflated to 2005 US$) for vaccination, influenza-related hospitalizations, physician and emergency visits, and the average wholesale price for prescription drugs and influenza vaccine. The base-case patient for the model was assumed to be a 67-year-old cancer patient (the median age at initial cancer diagnosis - all sites - for the 1998–2002 SEER population) with active disease. Results: The effectiveness of the no vaccination strategy was 4.665 QALYs at a cost of $95.23. The effectiveness of the influenza vaccine was 4.672 QALYs at a cost of $70.73. Thus, the vaccination strategy provided an incremental effectiveness of 0.007 QALYs over the no vaccination strategy at a reduction in cost of $24.50. Based on these gains, we estimate that vaccination of all adult cancer patients could potentially save third-party payers over $87 million in addition to gains in clinical benefits. The model was not sensitive to plausible changes in cancer survival, incidence of influenza, vaccine effectiveness, vaccine price, and risk of influenza-related hospitalization. Conclusions: Influenza vaccine is cost-effective for adult cancer patients. Health plans should expand their coverage to include the vaccine for adult patients with cancer. No significant financial relationships to disclose.
Association of low P27 with loss of hormone receptors in small (T1a/b) breast cancers
Authors: Wu J. , Mirchandani D. , Smith J. A. , Inghirami G. , Roses D. , Zeleniuch-Jacquotte A. , Muggia F. 
Published: March 2020

624 Background: P27kip1 is a nuclear protein that controls the cell cycle by inhibiting cyclin dependent kinases. In breast cancer cell lines, both estrogen and her-2/neu degrade p27 through the ubiquitin-proteasome pathway. T1N0M0 breast cancers with high p27 expression have excellent long-term survival (Loda et al, Cancer Research 1998), now we examine the association of low p27 and other prognostic factors in these patients. Methods: 122 T1N0M0 infiltrating ductal carcinoma were examined using immunohistochemistry. Specific monoclonal antibodies were used against estrogen receptor (ER), progesterone receptor (PR), Her-2/neu, p53 and p27. Percentage of cells stained were considered negative (or low for p27) if: ER <10%, PR <10%, p53<40%, her-2/neu DAKO score ≤ 1+, p27 (nuclear stain) <50%. Results: In T1a/bN0M0 tumors, 4/5 (80%) of low p27 tumors were also hormone receptor negative, while only 5/63 (8%) of the high p27 tumors were hormone receptor negative (P< 0.001, Fisher’s exact test). Although T1cN0M0 tumors showed a similar trend [4/12 (33%) of low p27 vs. 7/42 (17%) of high p27 tumors were hormone receptor negative], the difference was not statistically significant. No correlation was seen between low p27, her-2/neu, or p53 mutation. Conclusion: There is an association of low p27 and loss of hormone receptors in T1a/bN0M0 breast cancers, which may identify a subset of patients with a worse prognosis. Exploring the causes of p27 dysregulation (e.g., ubiquitin ligase overexpression) may shed further light on the significance of these associations. [Table: see text] No significant financial relationships to disclose.
Correlation of CA15.3 levels with clinical response in advanced breast cancer (ABC) patients receiving fulvestrant
Authors: Robertson J. F. , Agrawal A. , Gutteridge E. , Cheung K. , Evans A. J. 
Published: March 2020

641 Background: A transient initial rise (i.e. spike) in CA15.3 has been reported during treatment with anti-cancer therapies such as tamoxifen and chemotherapy. The spike may result from the partial agonistic and cytotoxic effects of these agents, respectively. Here, we report the clinical relevance of a transient initial rise in CA15.3 in patients treated with fulvestrant, an estrogen receptor (ER) antagonist with no agonist effects. Methods: Serial measurements of CA15.3 were made at regular intervals to monitor response in patients receiving fulvestrant 250 mg/month for the treatment of ABC. Marker profile at baseline, after 1, 3, 6, 9, and 12 months of treatment and at the time of progression was correlated with clinical benefit (CB) (complete response [CR]/partial response [PR]/stable disease ≥6 months) as per UICC criteria. Results: Sixty-seven patients (41 with metastatic breast cancer [MBC]; 26 with locally advanced primary breast cancer [LAPC]) with a median age of 72.9 years were treated with fulvestrant. CB was observed in 64.2% (n=43) with objective response (OR) in 19.4% (n=13). Median duration of clinical benefit (DoCB) was 26.6+ months. CA15.3 data at month 1 were available for 33 patients with CB. Eleven patients with CB (33.3%) had a rise in CA15.3 at month 1. Comparative responses in patients with and without spike phenomenon are shown in the Table . Five MBC patients with a spike in CA15.3 had an OR (CR=1; PR=4) compared with none of the MBC patients without a spike. Conclusions: Spike phenomenon is observed in more patients with MBC than patients with LAPC, which may reflect the overall tumor load in MBC patients. Higher OR rates were observed in MBC patients with spike phenomenon, but shorter DoCB. There was no apparent difference in ER status between patients with or without spike. Fulvestrant should not be stopped during the initial 1–2 months of treatment solely on the basis of a rising tumor marker, as a spike is observed in one-third of ABC patients who achieve CB with fulvestrant. [Table: see text] [Table: see text]