bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel intermediate endpoint for predicting overall survival in men with metastatic castration-recurrent prostate cancer (CRPC)
Authors: Halabi S. , Ou S. , Vogelzang N. J. , Scher H. , Small E. J. 
Published: March 2020

5113 Background: In this proposed study, we developed and validated a novel composite clinical benefit endpoint constructed from symptoms that have intrinsic clinical importance in 800 men with CRPC who were treated with front-line chemotherapy. Methods: Data from nine multimember trials (five phase II and four randomized phase III studies) conducted by the Cancer and Leukemia Group B (CALGB) from 1992–2004 were combined. Eligible patients had progressive adenocarcinoma of the prostate during androgen ablation (despite castrate testosterone levels), an ECOG performance status of 0–2, adequate hematologic, renal and hepatic functions. The tripartite composite clinical benefit endpoint (TCCBE) had three components: one based on disease progression (whether it be PSA, bone, or soft tissue progression), and the second based on weight loss (defined as at least 10% decline from baseline) or on performance status (PS) decline (by at least one level) to capture clinical deterioration. The third component was based on pain control and opioid analgesic use (no or yes). For a person to fall in the TCCBE “yes” category, at least two of the three components had to be recorded as no. For instance, if a patient at 3 months had no progression, no change in weight and did not use opioid analgesic, then he will be classified in the “yes” group and for the purpose of this analysis was considered as someone who achieved “clinical benefit”. The sample was randomly split into 526 (67%) and 274 (33%) men in the training and testing datasets, respectively. Results: From the training dataset, the median survival times in men who had and did not have clinical benefit were 20.9 months (95% confidence interval (CI) = 18.5–22.8) and 11.1 months (95% = 8.79–12.6, p- value<0.001). In the testing dataset, the median survival times in men with and without clinical benefit were 21.7 months (95% CI= 19.1–26.1) and 8.8 months (95% CI= 7.8–11.6) and in men. The hazard ratio (HR) for men with a clinical benefit compared to men without was 0.52 (95% CI= 0.43–0.62, P<0.001). Conclusions: The TCCBE is a statistically significant intermediate endpoint for predicting overall survival. Prospective validation of this endpoint is needed. No significant financial relationships to disclose.
Prevalence of osteoporosis and osteopenia during androgen deprivation (ADT) for prostate cancer: Baseline data from a large randomized controlled trial
Authors: Malkowicz S. B. , Chu F. , Forrest J. , Smith M. R. , Price D. , Sieber P. , Barnette K. G. , Rodriguez D. , Steiner M. S. 
Published: March 2020

5116 Background: Androgen deprivation therapy (ADT) is the standard treatment for men with advanced prostate cancer. ADT decreases bone mineral density (BMD) and increases fracture risk although there is limited information about the prevalence of osteopenia and osteoporosis during ADT. We evaluated the baseline data from a large fracture prevention study to better characterize the prevalence of ostepenia and osteoporosis in men receiving ADT for prostate cancer. Methods: In an ongoing phase 3 fracture prevention study, 1,392 men = 50 years old with histologically documented prostate cancer and receiving ADT were randomized to placebo or toremifene 80 mg, a selective estrogen receptor modulator. The phase 3 study included men at increased risk of fracture based on age = 70 years or low baseline BMD of the hip or spine as assessed by dual energy x-ray absorptiometry. Subjects with metabolic bone disease or receiving treatment for osteoporosis were excluded. In the current analyses, we report the baseline BMD and prevalence of osteopenia (T score -1.0 to -2.5 total hip, femoral neck or spine) and osteoporosis (T score = -2.5 total hip, femoral neck or spine) for the 1,139 subjects older than 70 years. The analyses were restricted to subjects =70 years because these subjects were included in the study regardless of baseline BMD. Results: Mean (± standard deviation) age was 76 ± 7 years. Mean duration on ADT was 39 ± 36 months. For men 70 years of age or older, mean T scores for the total hip, femoral neck, and spine are -1.01 ± 1.14, -1.50 ± 1.06 and 0.37 ± 1.88 respectively. A total of 73% of subjects 70 years of age or older were classified with osteopenia (55%) or osteoporosis (18%). Conclusions: In this large cross- sectional analysis, the vast majority of older men receiving ADT for prostate cancer have either osteopenia or osteoporosis. These observations provide further evidence that close attention to skeletal health is warranted during ADT for prostate cancer. No significant financial relationships to disclose.
Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery versus upfront surgery followed by chemotherapy (CT) in advanced epithelial ovarian carcinoma (EOC): A prospective randomized study—Interim results
Authors: Kumar Prof L. , Hariprasad R. , Kumar S. , Bhatla N. , Thulkar S. , Vijayaraghavan M. , Deo S. , Shukla N. , Singh R. 
Published: March 2020

5531 Background: To determine the impact of NACT on surgical debulking rate, overall and disease-free survival and quality of life (QOL) in patients with advanced EOC. Methods: Between Oct 2001 and Dec 2006, 128 previously untreated EOC patients (median age- 50 years, range 30 to 65) with FIGO stage III C & IV (pleural effusion only) have been randomized into - Arm A (n=65) upfront debulking Surgery followed by 6 cycles of Paclitaxel & carboplatin (PC) and Arm B (n=63): NACT with 3 cycles of PC followed by debulking Surgery then 3 more cycles. Eligibility criteria include - age 18 to 65 years, biopsy / cytological proven EOC, adequate hematological, renal, liver & cardiac functions, normal upper & lower GI endoscopy & CEA levels. Both groups were compared for debulking rate, duration of surgery, blood loss, intra & postoperative morbidity & mortality, overall response to treatment and QOL (FACT- O questionnaire). Results: 100 of 128 patients have completed treatment (arm A- 56, B-44). 7 patients were not evaluable; (Germ cell tumor-1, mixed Mullerian tumor-2, dual primary-1 and krukenburg-3). 93 patients are evaluable. Patients’ characteristics are similar in both arms. Grade III-IV - GIT (3% vs. 4%) & bone marrow (9% Vs 7%, p=ns) toxicity was similar in arm A & B, among 463 CT cycles administered. Patients in NACT arm had higher optimum debulking rate, p<. 0001, decreased blood loss during surgery (mean vol 520 vs 373 ml p<0.003) and reduced postoperative infections 14.8 % vs. 2.5%, p<0.04. Mean operative time (110 vs 95 minutes, p=0.12) and hospital stay (12 Vs 9.4 days, p=0.1) were similar in arm A & B. The median overall survival (arm A & B: 42 vs 29 months, p=0.07) and disease free survival (20 vs 25 months, p=0.11) is not different at a median follow up of 41 months. QOL score was significantly better in NACT arm at the end of treatment. (93 vs 114, p<. 001). Conclusions: Neoadjuvant chemotherapy in advanced epithelial ovarian cancer is associated with higher optimum debulking rate with reduced postoperative morbidity and improved quality of life. No significant financial relationships to disclose.
The comparison of accuracy between PET and PET/CT for detecting lymph node metastasis in cervical cancer: Prospective surgicopathologic study
Authors: Park J. , Seo S. , Kang S. , Lim S. , Lim M. , Choi H. , Kim S. , Yoo C. , Kim J. , Park S. 
Published: March 2020

5587 Background: Previosly, we reported the accuracy of positron emission tomography with 2-[fluorine18] fluoro-2-deoxy-D- glucose (FDG-PET) for detecting metastatic lymph node (LN) in cervical cancer (Eur J Cancer 2005: 41; 2086–92). The aim of this prospective study was to evaluate the accuracy of PET/CT for detecting lymph node metastasis in cervical cancer and to compare the accuracy between PET and PET/CT. Methods: From May 2002 to Jul 2006, 86 patients with untreated stage IB-IVA cervical cancer were enrolled. All patients underwent pretreatment clinical staging including PET (May 2002-Aug 2003, 54 patients) or PET/CT (Jan 2004-Jul 2006, 32 patients) followed by surgical staging including systematic pelvic and paraaortic lymph node (PLN and PALN) dissection. To enable region specific comparisons, PALN and PLN were divided into eight regions: both PALN, both common iliac areas, both external iliac areas, and both internal iliac/obturator areas. Each lymph node was sliced at 2-mm intervals perpendicular to the greatest dimension to maximize the likelihood of detecting micrometastases. All metastatic tumor size in each involved lymph node was measured. Histopathologic evaluation of lymph nodes was the diagnostic standard. The study protocol was approved by Institutioal Review Board, and a written informed consent was obtained. Results: A total of 688 LN regions were evaluated. The sensitivity, specificity, positive predictive value, and negative predictive value of PET and PET/CT are shown in Table 1 . As the metastatic tumor size increased, the sensitivity of PET and PET/CT was improved. Although there were no differences in sensitivity for detecting large sized (> 5mm or 10mm) metastatic tumor, PET/CT was more sensitive than PET for all pathologically proven LN metastasis which included small sized (< 5mm) metastatic tumor. Conclusions: PET/CT was more sensitive than PET for detecting small sized (<5mm) lymph node metastasis in cervical cancer. [Table: see text] No significant financial relationships to disclose.
Endometrial effects of exemestane compared to tamoxifen within the TEAM trial: Results of a prospective randomized study
Authors: Kieback D. G. , Harbeck N. , Bauer W. , Hadji P. , Weyer G. , Hasenburg A. 
Published: March 2020

572 Background: A prospective open label randomized multicenter substudy was performed in the German TEAM Trial Group to compare the effects of the irreversible aromatase antagonist Exemestane (EXE) and the ER agonist/antagonist Tamoxifen (TAM) on the endometrium during adjuvant treatment for postmenopausal estrogen receptor positive breast cancer. Methods: Transvaginal Ultrasound Scans (TVS) were performed at baseline, 6 and 12 months of treatment if no proliferation >5mm was present, and in 3 months intervals if endometrial thickness exceeded 5mm. Intent-to-treat analysis was performed based on 158 patients. Primary endpoint was the time interval from randomization to the earliest occurrence of endometrial hyperplasia > 10mm. Secondary endpoints were the time from randomization to endometrial hyperplasia > 5mm and the time interval from randomization to vaginal bleeding. Analysis of Time to Event Curves was performed by Kaplan-Meier method, analysis of differences between treatments by two-sided Logrank test and Cox Proportional Hazards. Differences in frequency were compared by Fisher‘s Exact Test. Results: 65 patients were available for analysis in the TAM arm, 78 in the EXE arm. Both groups were comparable regarding age, height, tumor grade,and stage. Median follow-up was 727 (EXE) and 526 days (TAM). In this time period, there were no (EXE) vs. 11 (TAM) cases of endometrial hyperplasia >10mm (p<0.0001), 11 (EXE) vs. 34 (TAM) patients with hyperplasia >5mm (p< 0.006). In total, endometrial hyperplasia was observed 11 times in the EXE arm vs. 45 times in the TAM arm (p<0.0001). Time to endometrial hyperplasia was significantly longer in the EXE group (p<0.0001); HR was 0.160 indicating an 84% risk reduction of hyperplasia in the EXE group. Increase in endometrial thickness from baseline to 6mo. was 2.94mm (EXE) vs. 5.41mm(TAM), from baseline to 12 mo 2.64mm vs. 6.0 mm respectively (p<0.0006). Only 1 patient underwent histological sampling in the EXE group (no hyperplasia) vs. 18 in the TAM subset. Conclusions: In a TEAM subprotocol, irreversible inactivation of aromatase by EXE resulted in significantly less endometrial proliferation than TAM during adjuvant therapy of receptor positive postmenopausal breast cancer. No significant financial relationships to disclose.
Prospective multicenter study of the impact of the 21-gene recurrence score (RS) assay on medical oncologist (MO) and patient (pt) adjuvant breast cancer (BC) treatment selection
Authors: Lo S. S. , Norton J. , Mumby P. B. , Smerage J. , Kash J. , Chew H. K. , Hayes D. , Epstein A. , Albain K. S. 
Published: March 2020

577 Background: The 21-gene RS assay has been validated to quantify the risk of distant recurrence in tamoxifen treated pts in N-ER+BC and predict magnitude of chemotherapy benefit. Since there is little data regarding the impact of RS on MO and pt decision making, this multi-center study was designed to prospectively examine whether RS affects MO and pt adjuvant treatment selection. Methods: MOs stated their treatment recommendation and confidence in it while pts indicated treatment choice pre and post RS assay. RS were returned to MO and pt for routine clinical care. Frequency distributions and co-frequency tables are used to display categorical distributions of nominal variables; means and standard deviations are used to summarize continuous variables. Results: 15 MOs at 1 community and 3 academic practices consecutively enrolled 93 pts (89 evaluable) with N-ER+BC. The treatment plan changed in 31.5% of MOs and 27% of pts. The frequency of treatment changes are in the table below. The largest change induced by RS results was conversion from pre-test CHT to post-test HT (22.5% of MO, 10.1% of pts). MOs stated RS results increased confidence in 68 (76%). 90% of pts felt the RS assay influenced their treatment choice; 95% were glad they took the test. Conclusion: The results of this study indicate that the RS assay does impact MO adjuvant treatment recommendations, pt treatment choice, and confidence in the treatment plan. Investigator initiated trial supported by an unrestricted clinical trial grant from Genomic Health Inc. [Table: see text] No significant financial relationships to disclose.
pKDR/KDR ratio predicts response in a phase I/II pharmacodynamic study of erlotinib and bevacizumab for recurrent or metastatic head and neck cancer (HNC)
Authors: Seiwert T. Y. , Davis D. W. , Yan D. , Mauer A. M. , Karrison T. , Kozloff M. , Dekker A. , Wong S. J. , Vokes E. E. , Cohen E. E. 
Published: March 2020

6021 Background: EGFR activation up-regulates VEGF, which has been correlated with resistance to anti-EGFR agents. We previously reported early results (Vokes, JCO, 2005) of a phase I-II study of the EGFR inhibitor erlotinib (E) with the VEGF antibody bevacizumab (B) in recurrent or metastatic HNC. We now present results from the pharmacodynamic analysis as well as updated outcome data. Methods: Phase I/II trial of fixed dose erlotinib (E) 150 mg orally daily with escalation of bevacizumab (B) to a maximum of 15 mg/kg q 3 weeks and continued at 15 mg/kg in the phase II portion. Pts were randomized to receive the initial bevacizumab dose on either day 1 or 15. Paired biopsies were taken at baseline and after 2 weeks of treatment (after E alone or E+B) and analyzed by immunofluorescence and laser scanning analysis for target inhibition and apoptosis markers (VEGFR2/KDR, EGFR, CD31, and respective activated forms [pKDR, pEGFR]). Results: Paired biopsies were available from 20 patients. At baseline pKDR/KDR (ratio) correlated with clinical outcome and differed significantly between responses (CR>SD: p<0.01; CR>PD: p<0.0005). Interestingly, endothelial cell EGFR levels also appeared to correlate with response (CR+SD>PD: p<0.03). Paired tissue samples showed that E or E +B treatment increased apoptosis in tumor cells (pre: 0.96%, post: 7.02%: p<0.05) and endothelial cells (pre: 0%, post: 12%: p=0.15). Further, E+B treatment reduced expression of endothelial KDR, EGFR and VEGF levels compared to E alone. We previously reported an overall response rate of 14.6% (48 evaluable patients in the phase II cohort). Updated median follow-up was 7.3 months (2.1 years for patients still alive). The updated median overall/ progression free survival was 7.3 months/ 3.9 months with 30.6%/ 8.2% of patients alive at 1/2 years. Conclusions: Compared to E alone the combination of E + B showed increased inhibition of endothelial survival factors. pKDR/KDR appears to predict response to E+B. The promising clinical efficacy of E+B and potential predictive biomarkers warrant further validation in larger cohorts. (Supported by NIH N01 CM-57018–16) No significant financial relationships to disclose.
Visits to urologists and radiation oncologists prior to treatment decision making for clinically localized prostate cancer (LCaP)
Authors: Jang T. L. , Bekelman J. E. , Liu Y. , Bach P. B. , Basch E. M. , Elkin E. B. , Zelefsky M. J. , Scardino P. T. , Begg C. B. , Schrag D. 
Published: March 2020

6506 Background: The two primary therapies for LCaP are delivered by different types of physicians, urologists and radiation oncologists. We evaluated how visits to various specialists relate to treatment choice. Methods: Using data from the Surveillance, Epidemiology and End Results (SEER)-Medicare linked program, we evaluated 85,088 men with LCaP aged 65 and older diagnosed between 1994 and 2002 who received either radical prostatectomy (n=18,201), radiotherapy (n=35,925), primary androgen deprivation therapy (n=14,021), or expectant management (n=16,941) within 9 months of diagnosis. Prostate cancer specialists were identified by Medicare claims or data from the AMA Physician Masterfile. Results: Table 1 shows a strong association between the different specialists consulted and primary therapy received. When men aged 65 to 69 saw only a urologist, 70% had a radical prostatectomy; when also seen by a radiation oncologist, 15% had a radical prostatectomy. We found greater than expected variation in the propensity of a particular urologist’s patients to undergo radiotherapy evaluation, suggesting that some men are seen by a radiation oncologist less frequently (and others more frequently) than would be explained by chance. Conclusions: Recognizing that prostate cancer specialists have different viewpoints on the most appropriate management strategy, it is imperative to ensure that all men have access to balanced information prior to definitive therapy. No significant financial relationships to disclose. [Table: see text]
Comparing two methods of meta-analysis in clinical research - individual patient data-based (IPD) and literature-based abstracted data (AD) methods: Analyzing five oncology issues involving more than 10,000 patients in randomized clinical trials (RCTs)
Authors: Bria E. , Gralla R. J. , Raftopoulos H. , Giannarelli D. 
Published: March 2020

6512 Background: Meta-analyses are one of the highest recommendations levels in Evidence-Based Medicine (EBM). Recently, meta-analyses have increased using either IPD or AD methods. Controversy exists regarding reliability, applicability and feasibility of the different methods to draw conclusions from conflicting RCTs and to estimate magnitude of benefit of different treatments. Methods: As seen in the table , we selected 5 major issues in 3 malignancies subjected to IPD meta-analysis, and then conducted AD meta-analyses from publications of the individual studies, using published methods (Bria, Cancer Treat Rev 2006). We required that >90% of patient numbers for both IPD and AD analyses be available. Event-based relative risk ratios (RRs) with 95% confidence intervals (CI) were derived. Fixed- and random-effect models, and absolute benefits (AB) were calculated. Correlations between IPD Hazard Ratios (HRs) and AD-RRs were estimated using a linear regression model according to Pearson (r) and R2 coefficients (parametric) and Spearman (Rho) coefficient (non- parametric). Results: Results are below. A strong linear correlation exists between IPD-HRs and AD-RRs (r=0.994, R2=0.989; p<0.001; Rho=1.00). Conclusions: The strong correlation supports using high quality meta-analyses with either method to resolve major issues. Differences exist between the methods: IDP is well-suited for sensitivity analyses and for hypothesis generation involving issues not originally anticipated; AD is a practical method allowing EBM to be applied rapidly to major issues in oncology in a timely fashion. No significant financial relationships to disclose. [Table: see text]
Quality of life (QOL) predicts for progression-free survival (PFS) in patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib compared to interferon-alpha (IFN-α)
Authors: Cella D. , Li J. Z. , Cappelleri J. C. , Bushmakin A. , Charbonneau C. , Kim S. T. , Chen I. , Michaelson M. D. , Motzer R. J. 
Published: March 2020

6594 Background: In a recent international, randomized phase III trial, sunitinib malate, an oral multitargeted receptor tyrosine kinase inhibitor of VEGFRs, PDGFRs, KIT, RET and FLT3 with both antitumor and antiangiogenic effects, was associated with statistically superior clinical efficacy and superior health-related QOL vs. IFN-a as first-line therapy in patients with mRCC (Motzer et al, Proc ASCO 2006;24:2s [Abstract LBA3]). Here we report a substudy of baseline QOL variables predicting PFS. Methods: 750 mRCC patients were randomized 1:1 to receive either sunitinib 50 mg orally once daily in repeated 6-week cycles (4 weeks on treatment followed by 2 weeks off) or IFN-a (9 MU via subcutaneous injection 3 times weekly). QOL was measured by the Functional Assessment of Cancer Therapy-General (FACT-G), the FACT-Kidney Symptom Index's Disease-Related Symptoms subscale (FKSI-DRS), and the patient self-rated overall health state (EQ-VAS) from the EuroQol Group's EQ-5D self-report questionnaire. For all QOL endpoints, higher scores indicated better outcomes (better QOL or fewer symptoms). Cox proportional-hazards model was used to test which baseline QOL variables predict PFS while controlling for other baseline demographic and clinical factors as well as treatment. Because the three QOL scores are correlated (r=0.61–0.69), three separate univariate models were fitted. Results and Conclusions: All three baseline QOL variables were predictive of PFS: better baseline FACT-G, FKSI-DRS and EQ-VAS scores were associated with longer PFS. When QOL and other baseline variables were controlled in the models, the superior treatment effect of sunitinib on PFS remained robust and large (See the table below). [Table: see text]