bluuebunny/crossref_metadata_2025_split huggingface dataset:
An open-label, randomized, phase III trial of zalutumumab, a human monoclonal EGF receptor (EGFr) antibody, versus best supportive care, in patients with noncurable squamous cell carcinoma (SCCHN) of the head and neck who have failed standard platinum-based chemotherapy (ZALUTE).
Authors: Machiels J. H. , Subramanian S. , Ruzsa A. , Repassy G. , Lifrenko I. , Flygare A. , Sorensen P. , Ehrnrooth E. , Baadsgaard O. , Clement P. M. 
Published: February 2017

LBA5506 Background: Zalutumumab is a novel, fully human IgG1 mAb targeting the EGFr that has shown encouraging activity in SCCHN. Methods: Patients with noncurable SCCHN with an ECOG PS of 0-2 and centrally documented radiographic progressive disease (PD) within 6 months after platinum-therapy were randomized between zalutumumab monotherapy and best supportive care (BSC) in a 2:1 ratio. Stratification parameter was ECOG PS. Methotrexate (MTX) was allowed in the BSC arm only. Individual dose-titration of zalutumumab was applied (max. exposure 16 mg/kg). The primary endpoint was overall survival (OS), with progression free survival (PFS) as the only secondary endpoint to be compared between groups, using log-rank test. 231 deaths were required to statistically differentiate OS between groups with 80% power. Results: 286 patients (34F, 252M) were randomized. The median age was 57 years (range 18-78), 65% had distant metastasis and 17% were ECOG PS 2, all similar between groups. 78% of patients in BSC arm received MTX. Although a median OS of 6.7 months was observed in the zalutumumab group compared to 5.2 in the BSC group, this was not statistically significant (p=0.065). A clear improvement in PFS (P=0.001) was demonstrated. Zalutumumab showed a safety profile as expected within this drug class. Conclusions: This is the first controlled study to demonstrate that an EGFr-targeted antibody given as monotherapy induces a clinically meaningful improvement in PFS in patients with SSCHN who have failed platinum-based chemotherapy. [Table: see text] [Table: see text]
Dasatinib compared to imatinib (IM) in patients (pts) with newly diagnosed chronic-phase chronic myelogenous leukemia in chronic phase (CML-CP): Twelve-month efficacy and safety from the phase III DASISION study.
Authors: Kantarjian H. , Shah N. P. , Hochhaus A. , Cortes J. E. , Shah S. , Ayala M. , Moiraghi B. , Bradley-Garelik M. , Zhu C. , Baccarani M. 
Published: February 2017

LBA6500 Background: Dasatinib is a highly potent BCR-ABL kinase inhibitor. Once daily dasatinib demonstrated high rates of durable complete cytogenetic response (CCyR) with 73% progression-free survival and 87% overall survival at 3 yrs in pts with CML-CP post IM failure. DASISION compares efficacy and safety of dasatinib and IM as initial treatment of CML-CP. Methods: 519 pts with Ph(+) newly diagnosed CML-CP stratified by Hasford risk were randomized to dasatinib 100 mg QD (n = 259) or IM 400 mg QD (n = 260). The primary endpoint was 12-mo rate of confirmed CCyR (cCCyR; CCyR on 2 consecutive analyses; any # of metaphases). Other endpoints were rates of and times to CCyR and major molecular response (MMR). Results: Pts characteristics were well balanced. Minimum follow-up was 12 mos; median treatment duration was 14 mos. 85% of dasatinib and 81% of IM pts remained on study. Median dose intensity was 99 mg/d for dasatinib and 400 mg/d for IM. cCCyR rate was superior for dasatinib vs IM (77% vs 66%, P = 0.0067). 12-mo CCyR and MMR rates ( Table ) were higher for dasatinib vs IM (CCyR: 83% vs 72%; MMR: 46% vs. 28%). MMR was obtained significantly faster with dasatinib (HR 2.0, P < 0.0001) as was CCyR (HR 1.5, P < 0.0001). Rates of transformation to AP/BC were 1.9% for dasatinib and 3.5% for IM. Grade 3/4 anemia (10% vs 7%) and neutropenia (21% vs 20%) were similar across arms; thrombocytopenia was more common for dasatinib (19% vs. 10%). Non-hematologic adverse drug reactions (all grades) in ≥10% of pts (dasatinib vs. IM) were fluid retention (19% vs 42%; including pleural effusion, all grade 1 or 2, 10% vs. 0%), nausea (8% vs. 20%), vomiting (5% vs. 10%), myalgia (6% vs.12%), muscle inflammation (4% vs. 17%) and rash (11% vs. 17%). Conclusions: Dasatinib showed significantly higher and faster rates of CCyR and MMR vs IM. Given the predictive value of 12-mo CCyR and MMR and the favorable tolerability of dasatinib, dasatinib may improve long-term outcomes in pts with newly diagnosed CML-CP. [Table: see text] [Table: see text]
Adjuvant therapy with pegylated interferon alfa-2b (36 months) versus low-dose interferon alfa-2b (18 months) in melanoma patients without macro-metastatic nodes: EADO trial.
Authors: Grob J. J. , Jouary T. , Dreno B. , Gutzmer R. , Hauschild A. , Leccia M. T. , Landthaler M. , Asselineau J. , Garbe C. , Pehamberger H. E. 
Published: February 2017

LBA8506 Background: Adjuvant therapy with low-dose adjuvant interferon alfa-2b (IFN) as well as with pegylated interferon alfa-2b (PEG-IFN) were both shown to be superior to observation in melanoma (M) patients (pts) without macro-metastatic nodes. However, the two strategies have never been assessed head to head. Weekly injection of PEG-IFN facilitates a longer duration of treatment which may be critical for benefit. We thus compared adjuvant therapy of flat low-dose PEG-IFN (36 months) versus low-dose IFN (18 months) in intermediate-risk M pts without macro-metastatic nodes. Methods: In this multicenter, open-label, prospective randomized phase III trial, pts with resected M ≥ 1.5 mm in thickness and without clinically detectable nodes were randomized either to IFN (3 MU subcutaneously [sc] 3 times a week for 18 months) or to PEG-IFN (100 mcg sc once weekly for 36 months). Sentinel node procedure (SNP) was not a standard in 2003 and thus was optional. Approach was consistent by center. Randomization was stratified for centers and SNP procedure. Primary endpoint was relapse-free survival (RFS), and secondary were distant metastasis-free survival (DMFS), overall survival (OS), and grade 3-4 severe adverse events (SAE). Sample size (890 pts) was calculated to detect a 10% difference (power >80%, type I error of 5%, 2-sided) for RFS. Analysis describes 5-year probability of survival. Comparisons were done by intent-to-treat using Cox proportional models. Results: Of 898 pts enrolled, 896 (443 PEG vs 453 IFN) were eligible for evaluation after a median follow-up of 4.7 years. SLNB was performed in 68.2% of pts. Neither RFS (PEG-IFN 66.2% vs IFN 64.8%, p=0.43; HR, 0.91; 95% CI, 0.73 to 1.15) nor DMFS (71.3% vs 72.6%, p=0.86; HR, 1.02; 95% CI, 0.80 to 1.32) or OS (77.0% vs 78.4%, p=0.55; HR, 1.09; 95% CI, 0.82 to 1.45) showed statistical difference. There was an excess of SAE grade 3-4 in PEG-IFN arm (44.6% vs 26.6% in the first 18 months) which impacted on median duration of treatment (17.8 months in IFN arm; 19.2 in PEG-IFN arm, with only 28% completing 36 months treatment). Conclusions: Flat low-dose PEG-IFN did not show superiority over conventional low dose IFN. Attempts to increase benefit by prolonging treatment with PEG-IFN over 3 years were hampered by a high rate of treatment discontinuation possibly linked to SAEs with PEG-IFN. [Table: see text]
PARAMOUNT: Phase III study of maintenance pemetrexed (pem) plus best supportive care (BSC) versus placebo plus BSC immediately following induction treatment with pem plus cisplatin for advanced nonsquamous non-small cell lung cancer (NSCLC).
Authors: Paz-Ares L. G. , De Marinis F. , Dediu M. , Thomas M. , Pujol J. , Bidoli P. , Molinier O. , Sahoo T. P. , Laack E. , Reck M. , Corral J. , Melemed S. A. , John W. J. , Chouaki N. , Zimmerman A. , Visseren Grul C. M. , Gridelli C. 
Published: February 2017

CRA7510 Background: The PARAMOUNT trial investigated whether pem continuation maintenance therapy improves progression-free survival (PFS) after pem-cisplatin induction therapy in patients (pts) with advanced nonsquamous NSCLC. Methods: In this double-blind, placebo-controlled trial, 939 pts participated in the induction phase, specified as four cycles of induction pem (500 mg/m2) and cisplatin (75 mg/m2) on day 1 of a 21-day cycle. Pts who had not progressed during pem-cisplatin induction and had an Eastern Cooperative Oncology Group performance status (PS) of 0/1 (n=539; 57.4%) were randomized (2:1, stratified for disease stage, PS, and induction response) to maintenance pem (500 mg/m2 on day 1 of a 21-day cycle) plus BSC (n=359) or placebo plus BSC (n=180) until disease progression. All pts received vitamin B12, folic acid, and dexamethasone. The primary endpoint was PFS (target: HR=0.65, two-sided alpha=0.05; 90% power with minimum of 238 events). Results: Pt characteristics were balanced between arms: median age=61 years; 58% male; 95% Caucasian; 32% PS 0; 91% stage IV; 87% adenocarcinoma; and 45% induction complete/partial response. Pem continuation maintenance resulted in a 36% reduction in the risk of progression (HR=0.64, 95% CI: 0.51-0.81; P=0.00025). The median independently reviewed PFS (472 pts, 297 events), measured from randomization, was 3.9 months (95% CI: 3.0-4.2) on the pem arm, and 2.6 months (95% CI: 2.2-2.9) on the placebo arm. The disease control rate (% pts with response/stable disease) was 71.8% on the pem arm, and 59.6% on the placebo arm (P=0.009). The drug-related serious adverse event (AE) rate was 8.9% on the pem arm, and 9.2% of pts had grade 3/4 laboratory Common Toxicity Criteria AEs. On the placebo arm, the rates were 2.8% and 0.6%, respectively. Discontinuations due to AEs were 5.3% on the pem arm, 3.3% on the placebo arm. Conclusions: PARAMOUNT met its primary endpoint and showed that pem continuation maintenance following pem-cisplatin induction is an effective and well tolerated treatment for pts with advanced nonsquamous NSCLC.
Barriers in providing breast and colorectal cancer survivorship care: Perceptions of U.S. primary care physicians (PCPs) and medical oncologists (MOs).
Authors: Virgo K. S. , Lerro C. C. , Klabunde C. N. , Earle C. , Ganz P. A. 
Published: February 2017

CRA9006 Background: Increased coordination among clinicians in cancer survivorship care is needed yet the literature suggests barriers remain due to a fragmented healthcare system. This is the first nationwide study of barriers PCPs and MOs perceive regarding breast and colorectal cancer survivorship care. Methods: The Survey of Physician Attitudes Regarding the Care of Cancer Survivors (SPARCCS) was mailed to a nationally representative stratified sample (N=5,275) of eligible American Medical Association member PCPs and MOs (N=3,596) providing care to cancer survivors, to permit comparisons of views regarding follow-up testing, roles, knowledge self-confidence, and perceived barriers. We analyzed physician-based barriers using weighted multinomial logistic regression models adjusted for physician demographics, reimbursement, training, and practice characteristics. Results: 2,202 physicians (1,072 PCPs and 1,130 MOs) responded (57.6% response rate; 65.1% cooperation rate). In weighted univariate analyses, PCPs were significantly more likely to report often/always ordering tests or treatments as malpractice protection, being concerned about missed care, and lacking adequate training to manage patient problems. MOs were more likely to report (often/always and sometimes) concerns about duplicated care and about which physician provides general preventive health care. In multivariate regression models, physician specialty remained significant for 3 of 5 physician-based barriers. MOs were less likely to report inadequate training (OR: 0.33, 95% CI: 0.22-0.49), less likely to often/always order extra tests due to malpractice concerns (OR: 0.53, 95% CI: 0.34-0.84), and more likely to report being often/always (OR: 1.97, 95% CI: 1.13-3.43) and sometimes (OR: 2.16, 95% CI: 1.60-2.93) uncertain who is providing general preventive care, compared to PCPs. Conclusions: MOs perceived different physician-based barriers as problematic in cancer follow-up care compared to PCPs. Alleviation of inadequate training, malpractice-driven test ordering, and preventive care delivery barriers may require education and provision of survivorship care plans.
The evaluation of flaxseed for hot flashes: Results of a randomized, controlled trial, NCCTG study N08C7.
Authors: Pruthi S. , Qin R. , Terstriep S. A. , Liu H. , Loprinzi C. L. , Shah T. R. C. , Tucker K. F. , Dakhil S. R. , Bury M. J. , Carolla R. L. , Steen P. D. , Vuky J. , Barton D. L. 
Published: February 2017

CRA9015 Background: Hot flashes are a common symptom during the menopause transition or following breast cancer treatment that can negatively impact the quality of life for many women. Preliminary data have suggested that flaxseed, a rich source of dietary lignans, may be a potentially effective treatment for hot flashes. Methods: A phase III randomized, placebo controlled trial was conducted to evaluate the efficacy of flaxseed in reducing hot flashes. Postmenopausal women were randomly assigned to a flaxseed bar (providing 410 mg of lignans) for 6 weeks vs a placebo bar. Participants completed daily prospective, self report hot flash diaries during the baseline week and then began eating one study bar per day for 6 weeks, while continuing to record their daily hot flashes. The intra-patient difference in hot flash activity between baseline and the last treatment week was the primary endpoint. Side effects of the bars were evaluated through self report and CTC assessment. Results: Between October and December 2009, 188 women were enrolled onto this trial. Mean hot flash scores were reduced by 4.9 units in the flaxseed group and 3.5 in the placebo group (p=0.29). In both groups, a little over a third of the women received a 50% reduction in their hot flash scores. Only one side effect was significantly different between groups, that being grade 1 pruritis, which was more common (7%) in the placebo group versus 1% in the flaxseed group. Both groups reported increased abdominal distension, flatulence, diarrhea and nausea. Adherence and ability to detect treatment assignment did not differ between groups. Conclusions: The results of this trial do not support the use of 410 mg of flaxseed lignans for the reduction of hot flashes. The gastrointestinal side effects seen in both groups were likely due to the fiber content in the flaxseed and placebo bars.
RTOG 0525: Molecular correlates from a randomized phase III trial of newly diagnosed glioblastoma.
Authors: Aldape K. D. , Wang M. , Sulman E. P. , Hegi M. , Colman H. , Jones G. , Chakravarti A. , Mehta M. P. , Andrews D. W. , Long L. , Diefes K. , Heathcock L. , Jenkins R. , Schultz C. J. , Gilbert M. R. ,   Radiation Therapy Oncology Group
Published: February 2017

LBA2000 Background: Formalin-fixed, paraffin embedded GBM tumor tissue, adequate for conventional MGMT methylation analyses, was required for entry onto the RTOG 0525 clinical trial. Methods: Four prognostic biomarkers were evaluated on a training set of 220 retrospectively obtained GBM samples, consisting of IDH1 mutation, the glioma-CpG island methylator phenotype (G-CIMP), a microarray-based mRNA panel and a novel MGMT promoter methylation assay. For each biomarker, 2 (IDH1 and mRNA) or 3 subgroups (G-CIMP and MGMT) were defined based on associations with overall survival. All combinations (36 possible) of each of the 4 biomarker-derived subgroups were then defined and compared with survival data and then consolidated into 4 risk groups. Once created in the training set, this model was applied to the RTOG 0525 samples (n=763) for external validation. Results: Application of the molecular risk classification to RTOG 0525 samples (left table) showed a highly significant survival association (p<0.001). When compared to the recursive partitioning analysis (RPA, table on right), this composite molecular classifier better identified patients with long term survival and appears to improve resolution by revealing an additional distinct risk group. The molecular classifier was prognostic in each of the treatment arms individually. Conclusions: Four distinct biomarkers or biomarker panels were tested in GBM. These biomarkers were compared with clinical outcome in a training set to optimize a method to combine them into a classifier. This classifier was then validated on a large sample set from a large phase III clinical trial. This composite panel may represent an improvement over the existing RPA with respect to risk stratification of patients for GBM. Additionally, it has the potential to impact future clinical trial designs and provide enhanced opportunities for personalization of therapy for GBM. Support: NCI U10 CA2121661, U10 CA37422, P50 CA127001. [Table: see text]
Exemestane for primary prevention of breast cancer in postmenopausal women: NCIC CTG MAP.3—A randomized, placebo-controlled clinical trial.
Authors: Goss P. E. , Ingle J. N. , Ales-Martinez J. , Cheung A. , Chlebowski R. T. , Wactawski-Wende J. , McTiernan A. , Robbins J. , Johnson K. , Martin L. , Winquist E. , Sarto G. , Garber J. E. , Fabian C. J. , Pujol P. , Maunsell E. , Farmer P. , Gelmon K. A. , Tu D. , Richardson H. 
Published: February 2017

LBA504 Background: Limited efficacy and serious toxicities have limited uptake of tamoxifen or raloxifene as preventatives of breast cancer. Aromatase inhibitors (AIs) prevent contralateral breast cancers more than tamoxifen in adjuvant trials and have fewer serious side effects. This is the first report of an AI used in primary prevention. Methods: NCIC CTG MAP.3 is a randomized trial designed to detect a 65% reduction in annual incidence of invasive breast cancer (IBC) on exemestane (E) versus placebo (P). Eligible postmenopausal women had ≥ one of the following risk factors: Gail score >1.66%, prior ADH, ALH, LCIS or DCIS with mastectomy, age over 60. Health-related and menopause-specific quality of life (QOL) were assessed by SF-36 and MENQOL questionnaires. Results: From 2004-2010, 4,560 women were randomized: age 62.5 yrs (37-90); Gail Score 2.3 % (0.6-21); BMI 28.0 kg/m2 (15.9-65.4). Risk factors included: age >60 yrs (49%); Gail score >1.66 (40%); and prior ADH, ALH, LCIS or DCIS with mastectomy (11%). At median follow-up of 35 months there were 11 IBCs on E and 32 on P (annual incidence 0.19% vs 0.55%; HR= 0.35, 95% CI 0.18-0.70, p = 0.002); ductal (10E/27P), lobular (1E/5P). Most tumors were ER positive (7E/27P); Her2/neu negative (10E/26P); TNM stage T1 (8E/28P), N0 (7E/22P), M0 (11E/30P). E was superior in all subgroups: by Gail score, age, BMI, prior LCIS and DCIS. The annual incidence rate of IBC or DCIS was 0.35% E and 0.77% P (HR=0.47;95% CI 0.27-0.79; p = 0.004) based on 64 IBCs or DCISs (20E/44P). Clinical bone fractures, osteoporosis, hypercholesterolemia or cardiovascular events were equal in both arms. No clinically meaningful differences in QOL were detected. Conclusions: Exemestane significantly reduced invasive and pre-invasive breast cancers in postmenopausal women at increased risk for breast cancer with no serious toxicities. Exemestane should be considered a new option for primary prevention of breast cancer. Supported by the Canadian Cancer Society; Pfizer Inc. PEG supported in part by Avon Foundation.
Clinical presentation of breast cancer: Age, stage, and treatment modalities in a contemporary cohort of Michigan women.
Authors: Smith D. R. , Caughran J. , Kreinbrink J. L. , Parish G. K. , Silver S. M. , Breslin T. M. , Pettinga J. E. , Mehringer A. M. , Wesen C. A. , Yin H. , Share D. , Davis A. T. , Pleban F. T. , Bacon-Baguley T. A. 
Published: February 2017

1 Background: The U.S. Preventative Services Task Force (USPSTF) revised their breast cancer screening recommendations in 2009 changing their stance on age and frequency of mammography screening to biannual exams starting at age 50. The purpose of this study is to analyze data from a statewide breast cancer registry managed by the Michigan Breast Oncology Quality Initiative (MiBOQI) to determine the impact of these new recommendations on diagnosing and treating breast cancer. Methods: De-identified data were collected on women participating in the MiBOQI registry at seventeen statewide institutions from 2006-2009. Data included method of detection, cancer stage, age at detection, treatment type, and patient demographics. Participants were stratified based on age, and data analyzed using NCSS software (chi-square and t-tests). Results:5903 women with breast cancer with an average age at diagnosis of 59.4 years were included. 65.5% of breast cancers were detected via mammography, 29.8% by palpation, and 4.7% by other methods. In women under 50 years of age, cancers were detected by mammography in 48.3% (69.3% >50yr) and by palpation in 46.1% (24.1% >50yr). Patients with palpable presentations were younger (55.8 yr vs. 61.2 yr; p <0.001). Cancers with a palpable presentation were diagnosed at higher stages (50.0% stage II) than with mammography (52.5% stage I; p<0.001). Breast conservation surgery occurred more frequently than mastectomy (palpation 54.2%; mammography 72.9%, p<0.001) but cancers detected through palpation were more likely to undergo mastectomy procedures. Conclusions: Results of this study validate the importance of annual screening mammography in women older than 50 years, and women aged 40 to 49 years recently omitted from screening guidelines. There was an increased prevalence of palpation for the method of detection in women less than 50 years of age. If screening mammography is omitted in this group, cancers when detected may be of a more advanced stage and result in more mastectomies. This study also supports the use of palpation as a method of detection despite recent recommendations against teaching self breast exams by USPSTF.
The impact of lymph node status on clinical outcomes following accelerated partial breast irradiation.
Authors: Shah C. , Wilkinson J. B. , Wallace M. , Vicini F. A. 
Published: February 2017

107 Background: Currently, node-positive patients are considered unsuitable for APBI per the ASTRO guidelines with limited data on outcomes of node-positive patients following APBI. Methods: 510 patients with early-stage breast cancer received accelerated partial breast irradiation (APBI) between April 1993 and November 2010. Of these, 39 were lymph node positive with 10 patients having N1mi disease (median size of mets = 0.82 mm) and 29 patients having N1 disease (61.5% had 1 node positive [median size of mets = 2.5 mm], 30.8% had 2 nodes positive [median size of mets = 8.0 mm], and 7.7% had 3 nodes positive [median size of mets = 20 mm]). Patient, clinical, and pathologic factors were analyzed and compared for the node-negative (N0) and node-positive (N+) cohorts including age, tumor size, receptor status, margin status, adjuvant hormone therapy, adjuvant chemotherapy, and length of follow-up. Results: N+ patients were younger (p=0.04), had larger tumors (p<0.001), and were more likely to receive chemotherapy (p<0.001). Median follow-up was 5.3 years for N0 patients and 5.9 years for N+ patients (p=0.06). At 5 years, no differences were seen in the 5-year actuarial rates of LR (2.2% v. 2.6%, p=0.86), AR (0% v. 0%, p=0.69), DFS (90.0% v. 88.0%, p=0.79), CSS (98.0% v. 90.0%, p=0.06), or OS (91.0 v. 84.0%, p=0.65) while higher rates of RR (0% v. 6.1%, p<0.001) and DM (2.2% v. 8.9%, p=0.005) were noted in N+ patients. A total of 10 LRs occurred in the N0 patients and 1 LR in the N+ patients at a median of 2.6 and 1.5 years respectively. Both RR that developed in N+ patients were within the supraclavicular fossa at a median of 2.8 years. Univariate analysis of LR was performed and age (p=0.31), tumor size (p=0.48), ER status (p=0.13), PR status (p=0.34), T-stage (p=0.48), chemotherapy (p=0.41), APBI technique (p=0.80), and nodal status (p=0.86) were not associated with LR while there was a trend for the association of LR with close/positive margins (p=0.07), and failure to receive adjuvant hormonal therapy (p=0.06). No variables were associated with any type of AR. Conclusions: No difference was seen in the rates of local recurrence or axillary failure between node-negative and node-positive following APBI with 5-years of follow-up.