bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase III study of lapatinib (L) plus trastuzumab (T) and aromatase inhibitor (AI) vs T+AI vs L+AI in postmenopausal women (PMW) with HER2+, HR+ metastatic breast cancer (MBC): ALTERNATIVE.
Authors: Gradishar William John , Hegg Roberto , Im Seock-Ah , Park In Hae , Tjulandin Sergei , Kenny Sarah , Sarp Severine , Williams Lisa , Izquierdo Miguel A. , Johnston Stephen R. D. 
Published: September 2018

1004 Background: Combination ofHER2-targeted therapy+AI improved clinical benefit in patients (pts) with HER2+, HR+ MBC vs AI alone in two previous trials, median progression free survival (mPFS) 4.8 vs 2.4 mo (TAnDEM), and 8.2 vs 3.0 mo (EGF30008). Dual HER2 blockade enhances clinical benefit vs single HER2 blockade. This study evaluated the safety and efficacy of dual vs single HER2 blockade (L+T vs T/L)+AI in HER2+, HR+ MBC progressing on (neo)adjuvant/first-line T+chemotherapy (CT). HER2 and HR status were assessed for eligibility at local lab. Methods: PMW were randomized 1:1:1 to receive T (8mg/kg followed by 6mg/kg IV Q3W)+L (1000mg/d)+AI or T+AI or L (1500mg/d)+AI. AI was per investigator’s choice. Pts were excluded if they were intended for CT. The primary endpoint was to assess superiority of PFS with L+T vs T. Secondary endpoints included PFS (L vs T), overall survival (OS), overall response rate (ORR), and safety. Results: 369 pts were enrolled; current analysis included 355 pts (data cutoff, March 11, 2016); L+T (n = 120), T (n = 117) or L (n = 118). Final PFS data were analyzed after 137 events. Baseline characteristics were balanced across all treatment (tx) arms. The primary endpoint was met; superior PFS was observed with L+T vs T (mPFS, 11 vs 5.7 mo; HR = 0.62, 95% CI [0.45, 0.88], P= 0.0064). This benefit of L+T was consistent in key subgroups. mPFS with L vs T was 8.3 vs 5.7 mo (HR = 0.71, 95% CI [0.51, 0.98], P= 0.0361). ORR with L+T, T, and L was 32%, 14%, and 19% respectively. OS data are immature. Most common adverse events (AEs) with L+T, T and L (≥15%, any arm) were diarrhea (69%, 9%, 51%), rash (36%, 2%, 28%), nausea (22%, 9%, 22%), and paronychia (30%, 0, 15%). Hepatic abnormalities of > 3 ULN ALT/AST levels were noted in 4%, 6%, and 16% respectively. Incidence of tx-related SAEs was 5%, 2%, and 4% and on-tx deaths was 3%, 4%, and 5%, respectively. Conclusions: Dual HER2 blockade with L+T+AI showed superior PFS benefit vs T+AI, in pts with HER2+, HR+ MBC. Incidence of AEs was increased with L+T. This combination can potentially offer an effective CT-sparing tx option in subgroup of HER2+, HR+ pts without aggressive disease and who are not candidates for CT. Clinical trial information: 2010-019577-16.
Serum frailty biomarkers to predict overall survival in older patients with metastatic solid tumors: A substudy of prospective multi-center cohort study (KCSG PC13-09).
Authors: Kim Se Hyun , Kim Jin Won , Hwang In Gyu , Jang Joung Soon , Hong Soojung , Kim Tae Yong , Baek Ji Yeon , Shin SeongHoon , Sun Der Sheng , Hong Dae Sik , Kim Hyo Jung , Hong Yong Sang , Lee Ju-Hyun , Woo In Sook , Kim Jee Hyun ,   Korean Cancer Study Group Geriatric Oncology Working Party
Published: September 2018

10041 Background: To determine individualized cancer treatment for older patients, easily measurable markers that predict functional decline and mortality are needed. The purpose of this study was to confirm prognostic value of potential biomarkers of frailty in older patients with metastatic solid tumors. Methods: Serum samples were prospectively collected before first line chemotherapy at 11 academic centers in Korea. All patients were participants in a prospective cohort study of older patients with metastatic solid tumors (KCSG PC13-09, WHO ICTRP number: KCT0001071). Serum levels of C-reactive protein (CRP), CXCL10, SIRT1, VEGF-A, Activin A, C-terminal telopeptide of type I collagen (CTx), total 25-hydroxyvitamin D (vitD) were measured by ELISA and IL-6, Myostatin, Irisin, FGF-19, FGF-21, FGF-23 by luminex mutiplex assay. Overall survival (OS) was studied by means of Kaplan-Meier, Log Rank and Cox methods. Results: Serum samples from 138 patients (median age: 75, range: 70-92) were collected from Feb 2014 to Dec 2016. During a median follow up time of 13.8 months, 72 (52.6%) patients had died. Among 13 serum markers, CRP (log-rank, P=0.006), Activin A (P=0.003), and Myostatin (P=0.043) were significantly correlated with OS in univariate analyses. In a Cox regression analysis, Activin A (HR 2.36, 95% CI 1.41-3.96; P=0.001) and Myostatin (HR 2.70, 95% CI 1.24-5.84; P=0.012) were significantly associated with OS after adjustment of other clinical factors (Age, Gender, ECOG PS, BMI, Geriatric assessment, Chemotherapy response, WBC, Albumin). Conclusions: In older cancer patients, high serum concentration of Activin A and Myostatin are predictive of poor OS. [Table: see text]
Psychosocial effects of the relaxation response resiliency program (SMART-3RP) in patients with MGUS and smoldering multiple myeloma: A waitlist controlled randomized clinical trial.
Authors: Denninger John W. , Laubach Jacob P. , Yee Andrew Jenho , O'Donnell Elizabeth , Macklin Eric A. , Perez Giselle Katiria , Traeger Lara N. , Chad-Friedman Emma , Proszynski Jacqueline , Jacquart Jolene , Goldman Roberta , Riklin Eric , Niles Halsey , Nehrt Emily M. , Chaukos Deanna C. , Richardson Paul G. , Raje Noopur S. , Fricchione Gregory L. , Park Elyse R. , Benson Herbert 
Published: September 2018

10051 Background: Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic clonal precursors to multiple myeloma, a hematological malignancy. Because observation is currently the standard of care, a diagnosis of MGUS or SMM can be associated with stress and worry about progression. We evaluated the efficacy of the evidence-based mind-body intervention, the Stress Management and Resiliency Training: Relaxation Response Resiliency Program (SMART-3RP) in reducing distress and stress reactivity in patients with MGUS and SMM. Methods: In participants diagnosed with intermediate or high risk MGUS or SMM, this randomized, waitlist controlled trial (Oct 2013 – Sep 2016) assessed distress (10-point scale) as the primary outcome and perceived stress (PSS-10), stress reactivity (MOCS-A), and mindfulness (FFMQ) as secondary outcomes and hypothesized mediators of distress reduction. We collected self-report measures at enrollment (T1), 3 months (T2), and 6 months (T3). The immediate treatment arm received the 8-session, 1.5 hour/week SMART-3RP group intervention from T1 to T2 and continued practicing skills from T2 to T3; the waitlist arm received the intervention from T2 to T3. Results: 93 participants (59% women) diagnosed with MGUS (n = 49) or SMM (n = 44) were randomized to immediate treatment (n = 45) or waitlist (n = 48). In an ITT analysis of immediate SMART-3RP vs. waitlist (T1-T2), we found significantly greater improvement in distress (-1.4 vs. -0.3, p = .04) and stress reactivity (0.39 vs. 0.02, p < .001), but not perceived stress (-3.9 vs. -2.2, p = .12) or mindfulness (2.4 vs. -0.1, p = .17). Improvements in stress reactivity were maintained for the immediate treatment group (T2-T3), but only partially for distress. Conclusions: The SMART-3RP, compared to waitlist, reduced distress in participants with intermediate or high-risk MGUS and SMM, with improvements in stress reactivity as a primary mediator of distress reduction. Participants strongly endorsed the intervention’s ability to enhance coping and reduce distress. Clinical trial information: NCT01955395.
Can exercise influence survival following breast cancer: Results from a randomised, controlled trial.
Authors: Hayes Sandra Christine , Steele Megan , Spence Rosa , Pyke Christopher , Saunders Christobel , Bashford John , Eakin Elizabeth 
Published: September 2018

10067 Background: Exercise for Health was a randomised, controlled trial designed to evaluate an 8-month translational exercise intervention, commencing 6-weeks post-surgery for newly diagnosed breast cancer. Outcomes for this follow-up exploratory analysis were overall- and disease-free survival. Methods: Consenting urban-based women (n = 194) were randomized to one of two exercise groups (intervention delivered either face-to-face or over the telephone) or a usual care group, while consenting rural/regional women (n = 143) were randomised to either the telephone-delivered exercise group or usual care group. For the purposes of these analyses, exercise groups and usual care groups were combined (exercise group, n = 207; usual care group, n = 130). Analyses were done on an intention-to-treat basis and trials were registered with the Australian New Zealand Clinical Trials Registry (ACTRN12606000233527; 12609000809235). Results: Participant disease and treatment characteristics were similar to the wider breast cancer population in Queensland, Australia, and 42% of the sample resided in rural or regional areas. After a median follow-up of 101 months, there were 15/130 (11.5%) survival events in the usual care group, compared with 11/207 (5.3%) events in the exercise group. Disease-free events for the usual care versus exercise group were 23/130 (17.7%) and 25/207 (12.1%), respectively. The corresponding unadjusted hazard ratio for the exercise group for overall survival was 0.45 (95% CI = 0.21-0.97; p = 0.037), and for disease-free survival was 0.66 (95% CI = 0.38-1.17; p = 0.155). Conclusions: Epidemiological evidence consistently shows a positive relationship between physical activity and survival post-breast cancer, but is unable to establish causality. These exploratory findings suggest that an exercise intervention delivered during and beyond conventional treatment for breast cancer and that was designed to cater for all women, irrespective of place of residence and access to medical services, has clear potential to influence survival. Clinical trial information: ACTRN12606000233527; 12609000809235.
Clinical, sociodemographic, and behavioral factors associated with cumulative burden of morbidity (CBM) among testicular cancer survivors (TCS) in the Platinum study.
Authors: Kerns Sarah L. , Fung Chunkit , Williams AnnaLynn , Abu Zaid Mohammad Issam , Sesso Howard D. , Monahan Patrick , Ardeshirrouhanifard Shirin , Feldman Darren R. , Hamilton Robert James , Vaughn David J. , Beard Clair , Huddart Robert Anthony , Kim Jeri , Kollmannsberger Christian K. , Sahasrabudhe Deepak M. , Morlang Ashley Amidon , Cook Ryan , Fossa Sophie D. , Einhorn Lawrence H. , Travis Lois B. ,   The Platinum Study Group
Published: September 2018

10075 Background: TCS are an important group in which to characterize late effects of cancer and its therapy given their young age at diagnosis and high cure rate. We comprehensively evaluated CBM and identified associated clinical, sociodemographic, and behavioral risk factors among TCS given cisplatin based chemotherapy in a multicenter study. Methods: TCS completed a comprehensive health questionnaire. Responses were grouped into 22 adverse health outcomes (AHO) and graded by severity. A CBM score was calculated based on AHO number and severity, following Geenen et al (JAMA 2007). Multivariable ordinal logistic regression examined the association of clinical, sociodemographic, and behavioral factors with CBM. Variable-based hierarchical clustering identified individual AHOs that co-occurred. Results: Among 1,215 TCS (median age at evaluation 38 y, range 19-68 y; time since chemotherapy 4.6 y), over 20% had a CBM score of high (17%), very high (4%) or severe (0.4%). Most TCS, however, had CBM scores of low (37%), medium (28%), very low (9%) or none (5%). In a multivariable model controlling for time since chemotherapy, older attained age (OR 1.2; 95% CI 1.1 - 1.3), being widowed/divorced/separated (OR 1.8; 95% CI 1.1 - 3.1), having less than college-level education (OR 1.7; 95% CI 1.3 - 2.2), being retired/on disability (OR 2.5; 95% CI 1.2 - 5.3), and receipt of 4 cycles of BEP vs. 4 cycles of EP or 3 cycles of BEP (OR 1.3; 95% CI 1.01 - 1.8) were associated with increased odds of a worse CBM score; vigorous exercise (OR 0.7; 95% CI 0.5 - 0.9) and non-white race (OR 0.6; 95% CI 0.4 - 0.9) were associated with decreased odds. A separate cluster analysis revealed five groups of AHOs: those known to be cisplatin-related (e.g. neuropathy, ototoxicity); metabolic abnormalities (e.g. hypercholesterolemia, diabetes); vascular damage (e.g. stroke); testicular cancer-related (e.g. hypogonadism); and other (e.g. thyroid disease). Conclusions: TCS with factors associated with worse CBM may be candidates for closer monitoring. If confirmed, our cluster analysis showing that groups of conditions tend to co-occur in TCS could provide guidance for survivorship care plans.
Scalp Cooling Alopecia Prevention trial (SCALP) for patients with early stage breast cancer.
Authors: Nangia Julie R. , Wang Tao , Osborne Cynthia R. C. , Niravath Polly Ann , Otte Kristen , Papish Steven W. , Holmes Frankie Ann , Abraham Jame , Goldfarb Shari Beth , Courtright Jay G. , Paxman Richard , Rude Mari , Hilsenbeck Susan G. , Osborne C. Kent , Rimawi Mothaffar F. 
Published: September 2018

10088 Background: Adjuvant chemotherapy decreases the risk of recurrence. However, it has distressing side effects, including alopecia. There are no randomized trials assessing modern scalp cooling to prevent alopecia, and success rates in non-randomized trials have varied. Methods: We conducted a multi-center randomized trial to evaluate the safety and efficacy of the Orbis Paxman Hair Loss Prevention System (OPHLPS) in reducing chemotherapy-induced alopecia. Women with stage I-II breast cancer planned to receive anthracycline- or taxane- based chemotherapy for at least four cycles were eligible and randomized in a 2:1 ratio to scalp-cooling or control. Scalp-cooling was done with the OPHLPS 30 minutes prior to, during and 90 minutes after each chemotherapy. The primary efficacy endpoints were hair preservation and device safety. We planned to enroll 235 subjects to provide 85% power to detect a 20% difference in hair preservation. Secondary endpoints included wig/scarf use and quality of life assessed by the EORTC QLQ-30, HADS and BIS. Subjects will be followed for 5 years for recurrence, overall survival, and site of recurrence. One interim analysis was planned to allow the study to stop early for efficacy after 142 subjects were enrolled and evaluable for the primary endpoint. To maintain the overall type 1 error rate, an O’Brien-Fleming spending function was used (interim boundary p = 0.0061). Results: This is the first randomized trial with modern scalp cooling in the world. For the interim analysis, 142 subjects were evaluable. Among them, 48 (50.5%) out of 95 in the cooling group and 0 (0%) out of 47 in the control group had hair preservation. The one-tailed p-value from the Fisher’s exact test is < 0.0001, which crosses the superiority boundary (p = 0.0061). Thus on 9/26/2016 the DSMB stopped the study early. The interim analysis was presented at SABCS 2016. There are 195 subjects enrolled on this clinical trial, and the final subject will be evaluable for the primary outcome February 2017. The final analysis will be presented. Conclusions: Our trial showed that scalp cooling using OPHLPS is highly effective in hair retention. Paxman Coolers has applied for FDA clearance for the OPHLPS based on the results of the interim analysis. Clinical trial information: NCT01986140.
Morphological correlates of oxaliplatin induced peripheral neuropathy assessed by magnetic resonance neurography.
Authors: Apostolidis Leonidas , Schwarz Daniel , Xia Annie , Weiler Markus , Heiland Sabine , Schlemmer Heinz-Peter , Jaeger Dirk , Bendszus Martin , Baumer Philipp 
Published: September 2018

10092 Background: Oxaliplatin induced peripheral neuropathy (OXA-PNP) is a frequent side effect of oxaliplatin containing chemotherapy protocols. It is commonly assessed clinically via physical examination and patient reported symptoms. Research has been impeded by the lack of objective tests to quantify OXA-PNP. Neurophysiological examination is time-consuming and can only cover a selected part of the examined nerve. The aim of this study was to investigate in-vivo morphological correlates of OXA-PNP by magnetic resonance neurography (MRN). Methods: 20 patients with mild to moderate OXA-PNP and 20 matched controls were prospectively enrolled. All patients underwent a detailed neurophysiology examination prior to neuroimaging. A standardized MRN imaging protocol at 3.0 Tesla with large-coverage included the lumbosacral plexus, as well as both sciatic nerves and their branches using T2-weighted fat-saturated sequences at high resolution. Qualitative evaluation of sciatic, tibial, and peroneal nerves were performed by two readers regarding the presence, degree, and distribution of nerve lesions. Quantitative assessment included volumetry of the dorsal root ganglia (DRG) and sciatic nerve normalized T2 (nT2) signal and caliber. Results: Significant DRG hypertrophy in OXA-PNP patients (207.3±47.7mm3 vs. 153.0±47.1mm3 in controls, p = 0.001) was found as morphological correlate of the sensory neuronopathy. Peripheral nerves only exhibited slight morphological alterations qualitatively. Quantitatively, sciatic nerve caliber was unchanged (26.0±5.1mm2 vs. 27.4±7.4mm2, p = 0.19) while sciatic nerve nT2 signal was slightly and non-significantly elevated in patients (1.32±0.22 vs. 1.22±0.26, p = 0.19). Conclusions: OXA-PNP leads to morphological correlates that can be detected in-vivo by MRN. Significant hypertrophy of the DRG was observed, a phenomenon which has not been described in OXA-PNP previously. DRG volume should be investigated as a biomarker in other sensory peripheral neuropathies and ganglionopathies as well as in studies evaluating neuroprotective strategies for OXA-PNP.
Use of heart rate variability (HRV) biofeedback for symptom management among cancer survivors.
Authors: O'Rourke Mark Allen , Franco Regina A. , Sofge Jameson , Ginsberg Jay , Susko Kerri , Crowley Elizabeth , Anderson Annie , Christ Alex , Hanna John , Hendry William , Burch James 
Published: September 2018

10099 Background: Late effects of cancer and its treatment include pain, fatigue, stress, and depression all mediated by autonomic dysfunction. Heart Rate Variability (HRV) coherence is an established measure of autonomic dysfunction. Cancer survivors have lower HRV coherence than normal controls. HRV biofeedback (HRV-B) training improves HRV coherence, restores autonomic health, and reduces the above symptoms. This report describes a feasibility study of HRV-B in symptomatic cancer survivors. Methods: In a randomized, waitlist controlled, clinical trial, 179 were screened, 34 enrolled and 31 completed the protocol. Participants in the intervention arm received weekly HRV-B training up to six weeks. Outcome measures assessed at baseline (pre) and after week six (post) included HRV coherence plus Insomnia Symptom Questionnaire (ISQ), Suscro Distress Inventory (SDI), Brief Pain Inventory (BPI), Multi-Dimensional Fatigue Inventory (MFI), Perceived Stress Scale (PSS) and Beck Depression Inventory II (BDI-II). Results: See table below. Conclusions: Delivering HRV Biofeedback training to cancer survivors is feasible at our Cancer Institute. This pilot study provides preliminary evidence that HRV-B for cancer survivors improves HRV coherence and reduces insomnia, pain, fatigue, depression, and stress. The intervention has great potential and further research is indicated. [Table: see text]
Everolimus (EVE) plus endocrine therapy in patients with estrogen receptor–positive (ER+), human epidermal growth factor receptor 2–negative (HER2−) advanced breast cancer (BC): First- and second-line data from the BOLERO-4 study.
Authors: Cardoso Fatima , Villanueva Cristian , Royce Melanie , Cruz Felipe , Debled Marc , Hegg Roberto , Toyama Tatsuya , Falkson Carla Isadora , Jeong Joon , Srimuninnimit Vichien , Ozguroglu Mustafa , Gradishar William John , Azevedo Sergio J , Arce Christina H. , Ridolfi Antonia , Lin Chinjune , Bachelot Thomas Denis 
Published: September 2018

1010 Background: Initial first-line (1L) data from the phase 2 BOLERO-4 (NCT01698918) study of EVE + letrozole (LET) in postmenopausal patients (pts) with ER+, HER2− metastatic BC (MBC) or locally advanced BC (LABC) have been previously reported. Here, we present updated 1L progression-free survival (PFS) data, plus new data describing second-line (2L) EVE + exemestane (EXE) in pts with disease progression after EVE + LET. Methods: Postmenopausal pts with ER+, HER2− MBC or LABC with no prior therapy for advanced disease received EVE 10 mg/day + LET 2.5 mg/day. After disease progression, pts could receive EVE + EXE 25 mg/day until further disease progression, unacceptable toxicity, or withdrawal of consent. Primary endpoint: 1L PFS. Secondary endpoints: overall response rate (ORR), clinical benefit rate (CBR), 2L PFS, overall survival (OS), and safety (1L and 2L). Results: Among 202 pts (median age, 64 years) with 1L MBC (96%) or LABC (4%), median PFS (95% CI) was 21.7 (18.123.9) months, ORR was 43.6%, and CBR was 74.3%. 42 pts (median age, 62 years) with MBC (88%) or LABC (12%) who progressed on 1L EVE + LET received optional 2L EVE + EXE. 2L median PFS (95% CI) was 3.7 (1.89.1) months, ORR was 4.8%, and CBR was 21.4%. Common 1L adverse events (all grades, regardless of drug relationship) were stomatitis (69%), weight loss (44%), diarrhea (40%), nausea (37%), and anemia (35%); 2L adverse events included stomatitis (19%) and weight loss (19%). Median duration of follow-up from start of 1L to the data cutoff for these new analyses (17 June 2016) was 23.5 months. OS will be analyzed at a later data cut. Conclusions: EVE + LET is an effective regimen in 1L ER+, HER2− advanced BC. Thesedata support previously reported BOLERO-2 data demonstrating a PFS improvement from addition of EVE to an aromatase inhibitor. 2L data, although limited by the small number of pts, show preliminary evidence of EVE activity when continued beyond disease progression. No new safety signals were seen. Lower rates of stomatitis in 2L were noted. Clinical trial information: NCT01698918.