bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breast cancer molecular profiles and tumor response of neoadjuvant doxorubicin and paclitaxel: The I-SPY TRIAL (CALGB 150007/150012, ACRIN 6657)
Authors: Esserman L. J. , Perou C. , Cheang M. , DeMichele A. , Carey L. , van 't Veer L. J. , Gray J. , Petricoin E. , Conway K. , Hylton N. , Berry D. 
Published: February 2017

LBA515 Background: I-SPY is a multi-center trial designed to identify predictive markers of pathological complete response (pCR) and survival of women with locally advanced breast cancers (3cm or greater). Women received neoadjuvant doxorubicin and cyclophosphamide then paclitaxel. Methods: 237 women enrolled, 216 completed serial imaging and core biopsies. Pre-treatment assays include: Agilent expression arrays, MIP aCGH, p53 gene chip and sequencing, IHC and reverse phase protein arrays (RPMA). Response to therapy was measured by serial MRI, pCR and residual cancer burden (RCB). Associations among molecular markers, pCR, RCB and survival were evaluated using chi-square test, Kaplan-Meier curves and log-rank test. Results: Median tumor size was 6cm, % pCR and RCB 0/1 was 27% and 36% for the entire study; % pCR rate for the 144 Agilent arrays was 25%. Distribution, rates of pCR and RCB 0/1 are shown in the Table for molecular and IHC markers. DFS and OS will be presented. Several molecular subtypes, including NKI 70 gene low, luminal A, 21 gene set low and IHC HR+, define 15–28% of patients with 3–10% pCR, yet excellent early survival. Wound healing, most discriminatory for prognosis, is not predictive of chemotherapy response. By RPMA, patients with pCR had increased phosphorylation of 4EBP1, eNOS, cAbl, STAT5, EGFR, AKT (p<0.05). In ER+ patients with poor MR response, pIRS, pIGFR, p706S were activated (p<0.05). RCB is a more refined way to measure pCR and was more predictive of DFS and OS (p=0.01) than pCR alone with a mean follow up of 3.9 years. MR volume is highly predictive of pCR and RCB. For specific subtypes, e.g. basal, RCB is predictive of DFS (p<0.00001). Conclusions: LABC have aggressive biology. Response to therapy and outcome can be predicted by many biomarkers. The I-SPY data set provides a platform to compare, contrast and combine marker signatures to tailor therapy and demonstrates the power of the neoadjuvant setting. Support: ACRIN U01 CA079778 ; CALGB CA31964, CA33601; NCI SPORE CA58207. [Table: see text] [Table: see text]
Carboplatin plus paclitaxel (CP) versus carboplatin plus stealth liposomal doxorubicin (CLD) in patients with advanced ovarian cancer (AOC): Activity and safety results of the MITO-2 randomized multicenter trial
Authors: Pignata S. , Scambia G. , Savarese A. , Sorio R. , Breda E. , Ferrandina G. , Gebbia V. , Musso P. , Gallo C. , Perrone F. 
Published: February 2017

LBA5508 Background: CP is standard first-line chemotherapy for AOC. MITO-2 (Multicentre Italian Trials in Ovarian Cancer) is an academic randomized phase III study testing whether CLD is more effective than CP. Methods: AOC patients (pts), stage IC-IV, aged≤75, ECOG PS≤2, were randomized to CP (C AUC5 + P 175 mg/m2,d1q21) or to CLD (C AUC5 + LD 30 mg/m2,d1q21), both for 6 cycles. Primary endpoint is progression-free survival (PFS). Secondary endpoints are overall survival, objective response rate (ORR), toxicity and quality of life. To have 80% power in detecting a 0.80 HR in PFS, with 2-sided α error 0.05, 632 events are needed and 820 pts were planned. Activity was evaluated according to RECIST, toxicity according to NCI-CTC. Activity analysis was not blinded and no confirmation of response was required. Results: From January 2003 to November 2007, 820 pts were randomized, 410 to each arm. Median age was 57 yrs (range 21–77). Stage III (60%) and IV (22%) were prevalent. As of March 30, 2009, with a median follow-up of 35 months, 530 events for PFS and 269 deaths have been recorded. Six cycles were received by 86% and 80% of pts, with CP and CLD respectively. With complete data for 97% of pts, 290 pts were eligible for activity analysis (≥1 target lesion). ORR was 59% with CP and 57% with CLD (p=0.70). In 182 pts with non-target lesions only, complete response was 33% with CP and 29% with CLD (p=0.64). In 168 pts with elevated CA-125 only, CA-125 normalization was obtained in 83% with CP and 86% with CLD (p=0.56). Toxicity data are complete for 97% of pts. Statistically significant differences in haematological toxicity (CP vs CLD) were: anemia all grades 59% vs 68%, grade (G) 3–4 4% vs 10%; thrombocytopenia all grades 19% vs 48%, G3–4 2% vs 16%. Statistically significant differences in non haematological toxicity were: hair loss 63% vs 14%; skin toxicity all grades 6% vs 20%, G3–4 0 vs 2%; diarrhea all grades 13% vs 6%; stomatitis all grades 9% vs 20%; neurotoxicity all grades 47% vs 15%, G3–4 3% vs 0.3%. Conclusions: CLD as first-line treatment of AOC produced a similar activity, with a different toxicity profile, compared to CP. Required events are awaited for final PFS analysis. Partially supported by Schering-Plough. No significant financial relationships to disclose.
A phase II trial of proton radiotherapy for medulloblastoma: Preliminary results.
Authors: Yock T. I. , Yeap B. Y. , Ebb D. , MacDonald S. M. , Pulsifer M. B. , Marcus K. C. , Tarbell N. 
Published: February 2017

CRA9507 Background: Pediatric medulloblastoma (MB) is commonly cured with surgery, chemotherapy and radiation. However, the late effects of radiotherapy can be disabling. Proton radiotherapy irradiates less normal tissue, which should result in fewer late side effects of treatment. The purpose of this study was to describe the clinical outcomes of proton radiotherapy. Methods: All patients had surgery of the primary tumor followed by proton radiotherapy with or without concurrent chemotherapy and adjuvant platinum based chemotherapy. CSI doses ranged from 18-36 GyE, median dose 23.4 GyE. The tumor bed or posterior fossa was brought to 54 GyE. Concurrent enrollment in COG or other protocols was allowed. All pathology and imaging was reviewed at MGH to confirm the diagnosis. Results: 60 patients with MB were prospectively enrolled from May 2003 to December 2009 and 59 were evaluable for this analysis. Median age 6.6 yrs, range 3.5 - 22 years; M/F ratio 1.3; standard risk (SR, 45) or high risk (HR, 14). The median follow-up is 16 months. Two-year overall survival (OS) and progression-free survival (PFS) for the entire group is 91% and 87%. Two-year OS for SR MB and HR MB is 92% and 87%. 54 pts have baseline (BL) neurocognitive testing and 19 pts (14 SR, 5 HR) have follow-up (FU) evaluations including FSIQ spanning at an average of 2 years. Mean FSIQ at BL and FU are 107 and 102 (paired t-test: 0.046). Endocrine late effects include 4 patients with growth hormone deficiency, 1 patient with central hypothyroidism and 2 other endocrinopathies. Audiology information will be presented. Conclusions: Early results of this prospective trial are promising for improving clinical outcomes in patients with medulloblastoma. [Table: see text]
Randomized phase III trial comparing adjuvant paclitaxel/gemcitabine/cisplatin (PGC) to observation in patients with resected invasive bladder cancer: Results of the Spanish Oncology Genitourinary Group (SOGUG) 99/01 study.
Authors: Paz-Ares L. G. , Solsona E. , Esteban E. , Saez A. , Gonzalez-Larriba J. , Anton A. , Hevia M. , de la Rosa F. , Guillem V. , Bellmunt J. 
Published: February 2017

LBA4518 Background: Approximately half of patients with resected invasive bladder cancer will die within the first three years after surgery due to disease relapse, most of the recurrences being systemic. We have studied in a randomized phase III trial the role of 4 courses of the PGC triplet as compared to observation in this clinical setting. Methods: Eligibility criteria included: (1) resected high-risk muscle invasive bladder carcinoma (pT3-4 and/or pN+), (2) ECOG PS 0-1, (3) adequate renal function (CrCl > 50 ml/min), (4) ≤ 8 weeks post-cystectomy, (5) no relevant co-morbidities, and (6) signed informed consent. Eligible patients were assigned to observation or 4 courses of PGC (P 80 mg/m2 d1 and 8, G 1000 mg/m2 d1 and 8 and C 70 mg/m2 d1) q21 days. The primary objective was overall survival (OS). Results: The study was open in July 2000 and prematurely closed due to poor recruitment in July 2007, with 142 patients randomized (74 to observation and to 68 to PGC treatment). Baseline characteristics were well balanced among study arms. Median age was 63 yrs, pT3-4N0: 44%, anyTpN+:56%, PS 0: 59%, median time cystectomy-randomization: 48 days (14-91). In the PGC arm 76% of pts completed all 4 courses of therapy. Main Gr 3-4 toxicities were neutropenia 41%, febrile neutropenia 8%, thrombocytopenia 14%, anemia 5%, fatigue 14%, alopecia 10%, vomiting 8%, renal 5%. There was one toxic death (sepsis). At a median follow up of 30 months (range 1-95), 69 patients have died (45 in control arm and 24 in PGC arm). OS (ITT population) was significantly prolonged in the PCG arm (median NR; 5yr OS: 60%) compared to observation (median 26m; 5yr OS: 31%) (p<0.0009). DFS (p<0.0001), TTP (p<0.0001) and disease specific survival (p<0.0002) were also superior in the PGC arm. Conclusions: The results of this study strongly suggest that adjuvant PGC improves OS and DFS following cystectomy in high risk invasive bladder cancer. As the study was prematurely closed, the power for firm conclusions is however limited. [Table: see text]
Evaluation of circulating tumor cell (CTC) enumeration as an efficacy response biomarker of overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC): Planned final analysis (FA) of COU-AA-301, a randomized, double-blind, placebo-controlled, phase III study of abiraterone acetate (AA) plus low-dose prednisone (P) post docetaxel.
Authors: Scher H. I. , Heller G. , Molina A. , Kheoh T. S. , Attard G. , Moreira J. , Sandhu S. K. , Parker C. , Logothetis C. , McCormack R. T. , Fizazi K. , Anand A. , Danila D. C. , Fleisher M. , Olmos D. , Haqq C. M. , De Bono J. S. 
Published: February 2017

LBA4517 Background: A preplanned interim analysis of COU-AA-301 showed that AA, a selective androgen biosynthesis (CYP17) inhibitor, significantly improves OS in mCRPC. This is the first phase III study to prospectively assess CTC as a surrogate biomarker as part of a regulatory qualification process, here using updated OS data. Methods: 1,195 patients (pts) with mCRPC post docetaxel were randomized 2:1 to AA (1 g QD) + P (5 mg BID) (n = 797) or placebo + P (n = 398). CTCs (screening and baseline [BL]; post BL at weeks 4, 8 and 12) were enumerated (cells/7.5 mL) at MSKCC and The ICR using CellSearch and analyzed with other prognostic covariates as dichotomous and continuous variables using updated OS data at 775 events (prior to crossover from placebo to AA). CTC (as part of a biomarker panel - LDH, PSA, Hg, AlkPhos) was examined as a surrogate for OS. Multivariate (Cox model) analyses were conducted. Results: At median follow up (FU) of 20.2 mo, the difference in median OS between the 2 groups improved from 3.9 to 4.6 mo (AA 15.8 mo vs placebo 11.2 mo; HR = 0.74; p < .0001). CTC counts were evaluated in 972 pts at screening and BL, 838 at 4 wks, 783 at 8 wks and 723 pts at 12 wks. High concordance between screening and BL values was observed (r = 0.83). CTC conversion using standard definition for unfavorable (CTC ≥ 5) and favorable (CTC < 5) counts was predictive of OS as early as 4 wks after treatment and its inclusion significantly reduced the treatment effect at all post-treatment time points (HR: from 0.74 to 0.97). A reduced model incorporating CTCs and LDH was developed. Conclusions: The magnitude of the treatment effect of AA on OS increased with longer FU. Using standard definition of CTC conversion, the biomarker panel demonstrated a level of surrogacy for OS by correlating well with survival and in a model-adjusted analysis dramatically attenuating the treatment effect. BL CTCs and CTC conversion, along with LDH, were key predictors of OS. Future trials will further evaluate the CTC-based surrogate developed from COU-AA-301.
Accuracy of stereotactic vacuum-assisted biopsies in a community population.
Authors: Edwards S. D. , Vossen J. A. , Pronovost M. , Reeser P. 
Published: February 2017

106 Background: Stereotactic core biopsy in mammographically detected lesions permits histologic confirmation previous to surgery planning. We evaluated the use of stereotactic vacuum-assisted biopsy (VAB) for diagnosing suspicious, mammographically detected breast lesions in a community population. Furthermore, we determined the level of agreement between the pathology findings of VAB and the final surgical excisional biopsy. Methods: We retrospectively evaluated the results of 128 consecutive stereotactic VAB with 9-gauge needles performed over a period of 1 year in our community population. The imaging histologic concordance was ascertained for each lesion. We also evaluated concordance between VAB results and surgical excision results. Results: For the 128 patients included Breast Imaging Reporting and Data System (BI-RADS) staging showed BI-RADS 3: 4%; BI-RADS 4: 91%; and BI-RADS 5: 5%. VAB demonstrated 65 (51%) benign lesions, 31(24%) indeterminate lesions and 32 (25%) malignant lesions. The 31 indeterminate lesions included atypical ductal hyperplasia (n=13), lobular neoplasia (n=4), papillary lesions (n=12), radial sclerosing lesions (n=5), and flat epithelial atypia (n=13). Surgical excision was performed on 52 patients, and pathology demonstrated; 4 benign, 19 indeterminate, and 29 malignant lesions. There was one (3%) underestimation of an indeterminate lesion and there were 8 (25%) underestimations of malignant lesions after surgical excision. We did not observe any post-biopsy complications. Conclusions: Stereotactic VAB with a 9-gauge needle is a reliable method for diagnosing mammographically detected breast lesions in a community population.
Patient characteristics associated with the decision to undergo bilateral prophylactic mastectomy for lobular carcinoma in situ.
Authors: Muhsen S. , Junqueira M. J. , Park A. , Sung J. S. , Patil S. , Oskar S. , Morrogh M. , Morrow M. , King T. A. 
Published: February 2017

148 Background: Women at increased risk for breast cancer due to a diagnosis of lobular carcinoma in situ (LCIS) have three management options: high risk surveillance +/- chemoprevention (CP) or bilateral prophylactic mastectomy (BPM). Among a large cohort of women with LCIS, we previously reported there were no differences between women choosing CP compared to those choosing surveillance alone. The purpose of this study was to identify patient factors associated with the decision to pursue BPM for LCIS. Methods: We reviewed our prospectively maintained LCIS database to identify women choosing BPM (1995-2009). Comparisons were made between patients who chose BPM versus those who chose high risk surveillance +/- CP. Results: Among 995 pts with LCIS, 795 (80%) chose surveillance alone, 149 (15%) chose CP and 51 (5%) chose BPM. Compared to patients electing surveillance +/- CP patients who pursued BPM were younger at age of LCIS diagnosis (48 vs. 52 yrs, p < 0.001), more likely to have bilateral biopsies with LCIS (14% vs. 3%, p = 0.002) and more likely to be premenopausal (82% vs. 57%, p < 0.001). Patients choosing BPM were also more likely to have additional risk factors for breast cancer including: stronger family histories and extremely dense breasts (Table). Occult breast cancer was found in 4 (8%) BPM patients. At a median follow-up of 54 months (range 0-190 mos), 120/944 (13%) patients in the surveillance +/- CP group developed breast cancer. Conclusions: High-risk surveillance alone is the preferred management option for women with LCIS at our institution. Patients electing BPM are younger and more likely to have other associated risk factors for developing breast cancer. Further research to define how the increased risk imparted by LCIS is augmented by these factors may allow for better risk stratification and more informed discussions with patients. [Table: see text]
Number needed to treat and treatment cost per fracture avoided with denosumab compared with zoledronic acid in patients with breast cancer with bone metastases.
Authors: Wu E. Q. , Xie J. , Signorovitch J. , Diener M. , Sorg R. , Namjoshi M. 
Published: February 2017

151 Background: Pathologic fractures (PF) are a common and expensive-to-treat skeletal-related event (SRE), which affect over two-thirds of metastatic breast cancer (MBC) patients, and cost $26,936 (2009 US dollars) per event on average for inpatient treatment. In a phase III trial ( NCT20050136 ), MBC patients randomized to denosumab (Dmab; n=1,026) demonstrated longer time to SRE, but comparable rates of survival and disease progression relative to those randomized to zoledronic acid (ZOL; n=1,020). We calculated the number needed to treat (NNT) to avoid one PF and the treatment cost per PF avoided with Dmab vs. ZOL in MBC patients. Methods: Phase III trial results from the Dmab product label were used to determine the rate of PFs and SREs in MBC patients treated with Dmab vs. ZOL. Treatment cost included only the wholesale acquisition cost of Dmab and ZOL, and assumed 12 months of treatment. The NNT calculated the number of patients who would need to be treated with Dmab vs. ZOL to avoid one additional PF. Sensitivity analyses included expanding the treatment outcome from PFs to SREs and adding drug administration costs for Dmab and ZOL, and, renal monitoring costs only for ZOL. Results: Based on the estimated differences in PF risk of 2.7%, 37.4 patients would need to be treated with Dmab vs. ZOL to avoid one additional PF, resulting in a treatment cost per PF avoided of $346,911. The lower 95% confidence limit for the cost per PF avoided with Dmab vs. ZOL was $148,114, which is significantly greater than the mean inpatient cost of treating a PF event. Including drug administration and renal monitoring costs led to a cost per PF avoided of $323,069. Expanding the treatment outcome from PFs to SREs showed that 17.3 patients would need to be treated with Dmab vs. ZOL to avoid one additional SRE (95% CI: 10.2 to 59.7; absolute risk reduction 5.8%), resulting in a treatment cost of $160,595 per SRE avoided. Conclusions: PFs have a debilitating effect on patients, and treatment with Dmab compared to ZOL was associated with a treatment cost per PF avoided that exceeded 12 times the mean inpatient cost of a PF. Decision makers need to consider the high costs associated with Dmab prior to formulary inclusion.
Weight change associated with anastrozole and tamoxifen treatment in postmenopausal women with breast cancer or at high risk of developing it.
Authors: Sestak I. , Harvie M. , Howell A. , Forbes J. F. , Dowsett M. , Cuzick J. M. 
Published: February 2017

165 Background: Weight gain is commonly reported by patients with breast cancer. Aromatase inhibitors are being tested in the preventive setting in high risk women and it is important to evaluate the association between treatment and weight change as this may effect the patient’s decision to continue to take the drug. Methods: Weight change in postmenopausal women from three large clinical trials (ATAC, IBIS-I, IBIS-II) investigating endocrine treatment for the treatment and prevention of breast cancer have been analysed. The objective of this retrospective study was to assess the effects of anastrozole and tamoxifen on weight change in postmenopausal women. Results: In the ATAC trial, a mean increase of 1.4 kg was observed after 12 months of follow-up and no statistically significant differences between treatment arms (anastrozole vs. tamoxifen) were found. The majority of women kept their weight stable and only 11.2% gained more than 5 kg within this time period. Significant baseline predictors for gaining more than 5 kg of weight after 12 months of follow-up were being younger than 60 years old at entry, smoking at entry, and mastectomy. Results for the two prevention studies IBIS-I and IBIS-II were quite similar. In the IBIS-II trial, the overall mean weight change after 12 months of follow-up was 0.5 kg. In the IBIS-I study women gained an average of 0.9 kg within the first 12 months of follow up. In both studies no differences between treatment and placebo (IBIS-I: tamoxifen vs. placebo; IBIS-II: anastrozole vs. placebo) were observed. Overall, women in the adjuvant setting gained more than 5 kg of weight (11.2%) after 12 months of follow up compared to those in the preventive setting (5.3% IBIS-I, 5.7% IBIS-II), but similar overall weight gain was seen after 60 months of follow up in both settings (5.7% IBIS-I vs. 6.1% ATAC). Conclusions: All three trials have demonstrated that weight gain occurs primarily within the first 12 months of active treatment and are similar to those on placebo. Weight stabilises after 12 months of follow up and major weight gain was rare in all trials, and unrelated to treatment.
Change in patient-reported outomes over time from breast cancer diagnosis.
Authors: Hill-Kayser C. E. , Vachani C. , Hampshire M. K. , Di Lullo G. A. , Metz J. M. 
Published: February 2017

210 Background: Breast cancer survivors may be at risk for significant late effects after treatment. Understanding the patterns of change over time of patient reported outcomes (PRO) is often very challenging. Methods: Patient-reported data was gathered via a convenience sample frame from breast cancer survivors utilizing a publically available, free, Internet-based tool for creation of survivorship care plans. Available at www.livestrongcareplan.com and through the OncoLink website, the tool allows survivors to enter data regarding diagnosis, demographics, treatments received, and late effects experienced, and provides them with customized guidelines for future care. All data has been maintained anonymously with IRB approval. Results: 1,145 breast cancer survivors were queried with regard to PRO. Median age at diagnosis (dx) was 49 yrs, and median current age 52 yrs. Of users, 98% reported having had surgery; of these 56% underwent mastectomy and 49% lumpectomy (5% both). Similarly, 59% underwent sentinel LN biopsy, and 47% axilary dissection. Of the same cohort, 88% received chemotherapy and/or hormonal treatment, and 70% radiation therapy. The median time from dx until use of the care plan tool was 2 years (range 0-33 years). Late effects reported by survivors ≤ 2 and > 2 years from diagnosis are shown (see table). Overall, survivors ≤ 2 years from dx were more likely to note changes in skin color or texture; those > 2 years from diagnosis were more likely to note osteopenia, lymphedema, and sexual changes. Patient reported cognitive changes, arm pain/numbness/tingling, and loss of shoulder flexibility did not differ between the two groups. Conclusions: This anonymous tool uses a convenience sample frame to gather PRO after breast cancer diagnosis/ treatment. PRO varied significantly with time since dx, with more late effects reported > 2 years from dx. This information may be of use during patient counseling and survivorship care delivery. [Table: see text]