bluuebunny/crossref_metadata_2025 huggingface dataset:
“It Was Really Tough”—Exploring the Feelings of Isolation and Cultural Dissonance With Black American Males at a Predominantly White Institution
Authors: Patterson Anthony F.
Published: September 2018

Black American males and low socioeconomic status students face a gauntlet of obstacles when pursuing their college degrees. These young men do not earn degrees at the same rate as their peers. As campus engagement, recreation, and leisure play pivotal roles in students’ experiences, investigating their influence relative to social integration might facilitate a better understanding of the issues they face. This study explored how Black American male undergraduates from low socioeconomic status backgrounds perceived the roles that campus engagement, recreation, and leisure played in their social integration. Bronfenbrenner’s ecological model of human development guided the qualitative approach to this study. Seventeen participants were interviewed, and interwoven themes related to feelings of isolation and cultural dissonance emerged. Theorizing about the complex roles leisure plays, in some cases, creating isolation and cultural dissonance and, in others, helping students navigate the challenges of college are presented.
Memory encoding of syntactic information involves domain-general attentional resources: Evidence from dual-task studies
Authors: Heyselaar Evelien , Segaert Katrien
Published: September 2018

We investigate the type of attention (domain-general or language-specific) used during syntactic processing. We focus on syntactic priming: In this task, participants listen to a sentence that describes a picture (prime sentence), followed by a picture the participants need to describe (target sentence). We measure the proportion of times participants use the syntactic structure they heard in the prime sentence to describe the current target sentence as a measure of syntactic processing. Participants simultaneously conducted a motion-object tracking (MOT) task, a task commonly used to tax domain-general attentional resources. We manipulated the number of objects the participant had to track; we thus measured participants’ ability to process syntax while their attention is not taxed, slightly taxed, or overly taxed. Performance in the MOT task was significantly worse when conducted as a dual task compared with as a single task. We observed an inverted U-shaped curve on priming magnitude when conducting the MOT task concurrently with prime sentences (i.e., memory encoding), but no effect when conducted with target sentences (i.e., memory retrieval). Our results illustrate how, during the encoding of syntactic information, domain-general attention differentially affects syntactic processing, whereas during the retrieval of syntactic information, domain-general attention does not influence syntactic processing.
The Role of Visual Information in Body Size Estimation
Authors: Thaler Anne , Geuss Michael N. , Mohler Betty J.
Published: September 2018

The conscious representation of our physical appearance is important for many aspects of everyday life. Here, we asked whether different visual experiences of our bodies influence body width estimates. In Experiment 1, width estimates of three body parts (foot, hips, and shoulders) without any visual access were compared to estimates with visual feedback available in a mirror or from a first-person perspective. In the no visual access and mirror condition, participants additionally estimated their head width. There was no influence of viewing condition on body part width estimates. Consistent with previous research, all body part widths were overestimated with greater overestimation of hip and head width. In Experiment 2, participants estimated the size of unfamiliar noncorporeal objects to test whether this overestimation was partially due to the metric body size estimation method or our experimental conditions. Object width was overestimated with visual feedback in a mirror available as compared to when directly looking at the object, but only for objects placed at shoulder and head height. We conclude that at least some of the overestimation of body part width seems to be body specific and occurs regardless of the visual information provided about the own body.
Too Much Medicine: Behavioral Science Insights on Overutilization, Overdiagnosis, and Overtreatment in Health Care
Authors: Shaffer Victoria A. , Scherer Laura D.
Published: September 2018

Overutilization—defined as the use of health care services for which the benefits do not outweigh the harms—has been identified as one of the leading contributors to the rising cost of health care in the United States. Although informational interventions designed to address overutilization have had a significant, but modest, impact on the rate of overutilization, they have not been sufficient to solve the problem. Also, various psychological mechanisms contribute to the desire for more medical tests and treatments. To effectively address overutilization, we need to better understand the psychological underpinnings of overuse in medicine. The article reviews recent findings from the behavioral science literature—including reliance on anecdotal evidence, test-related affect, the use of diagnostic labels, and medical maximizing tendencies—that lend insight into why patients sometimes seek, demand, or expect medical tests and treatments that are considered by experts to be low value.
Immune checkpoint inhibitors as a bridge to allogeneic transplantation with posttransplant cyclophosphamide
Authors: Schoch Laura K. , Cooke Kenneth R. , Wagner-Johnston Nina D. , Gojo Ivana , Swinnen Lode J. , Imus Philip , Fuchs Ephraim J. , Levis Mark , Ambinder Richard F. , Jones Richard J. , Gladstone Douglas E.
Published: September 2018

Key Points

Checkpoint inhibition use before alloBMT followed by PTCy is not associated with increased aGvHD or transplant-related mortality/morbidity. Prior checkpoint inhibitor therapy should not be a contraindication to allogeneic transplantation, especially in the setting of PTCy.
The DNA repair transcriptome in severe COPD
Authors: Sauler Maor , Lamontagne Maxime , Finnemore Eric , Herazo-Maya Jose D. , Tedrow John , Zhang Xuchen , Morneau Julia E. , Sciurba Frank , Timens Wim , Paré Peter D. , Lee Patty J. , Kaminski Naftali , Bossé Yohan , Gomez Jose L.
Published: September 2018

Inadequate DNA repair is implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the mechanisms that underlie inadequate DNA repair in COPD are poorly understood. We applied an integrative genomic approach to identify DNA repair genes and pathways associated with COPD severity.

We measured the transcriptomic changes of 419 genes involved in DNA repair and DNA damage tolerance that occur with severe COPD in three independent cohorts (n=1129). Differentially expressed genes were confirmed with RNA sequencing and used for patient clustering. Clinical and genome-wide transcriptomic differences were assessed following cluster identification. We complemented this analysis by performing gene set enrichment analysis, Z-score and weighted gene correlation network analysis to identify transcriptomic patterns of DNA repair pathways associated with clinical measurements of COPD severity.

We found 15 genes involved in DNA repair and DNA damage tolerance to be differentially expressed in severe COPD. K-means clustering of COPD cases based on this 15-gene signature identified three patient clusters with significant differences in clinical characteristics and global transcriptomic profiles. Increasing COPD severity was associated with downregulation of the nucleotide excision repair pathway.

Systematic analysis of the lung tissue transcriptome of individuals with severe COPD identified DNA repair responses associated with disease severity that may underlie COPD pathogenesis.
Characteristics of patients expressing an interest in ketamine treatment: results of an online survey
Authors: Veraart Jolien K. E. , Smith-Apeldoorn Sanne Y. , Trueman Hayley , de Boer Marrit K. , Schoevers Robert A. , McShane Rupert
Published: September 2018

Background

Off-label ketamine treatment has shown acute antidepressant effects that offer hope for patients with therapy-resistant depression. However, its potential for integration into treatment algorithms is controversial, not least because the evidence base for maintenance treatment with repeated ketamine administration is currently weak. Ketamine is also a drug of misuse, which has raised concerns regarding the target population. Little is known about which patients would seek ketamine treatment if it were more widely available.

Aims

To explore some of the characteristics of the patients actively seeking ketamine treatment.

Method

An online survey containing questions about duration of current depressive episode, number of antidepressants used and other comments was completed by patients who were exploring the internet regarding the possibility of ketamine for depression.

Results

Of the 1088 people who registered their interest, 93.3% reported depression, 64.3% reported a chronic course of their symptoms and in the past 10 years, 86.3% had tried at least two antidepressants. Desperation was a common theme, but this appeared to be competently expressed. A small minority (<8%) reported experience of illegal ketamine use.

Conclusions

It cannot be ruled out that patients with different degrees of treatment resistance and comorbidities will seek treatment with ketamine. This stresses the urgency to perform larger randomised controlled trials as well as to systematically monitor outcomes and adverse effects of ketamine, that is currently prescribed off-label for patients in need.

Declaration of interest

R.M. is consulting and is Principal Investigator for Janssen trials of esketamine and is consulting for Eleusis.
MONARCH 2: Abemaciclib in combination with fulvestrant in patients with HR+/HER2- advanced breast cancer who progressed on endocrine therapy
Authors: Sledge George W. , Toi Masakazu , Neven Patrick , Sohn Joohyuk , Inoue Kenichi , Pivot Xavier B. , Burdaeva Olga Nikolaevna , Okera Meena , Masuda Norikazu , Kaufman Peter A. , Koh Han A. , Grischke Eva-Maria , Frenzel Martin , Lin Yong , Barriga Susana , Smith Ian C. , Bourayou Nawel , Llombart-Cussac Antonio
Published: September 2018

1000

Background: Abemaciclib, an oral, selective inhibitor of CDK4 & 6, dosed on a continuous schedule, demonstrated clinical activity as monotherapy in patients (pts) with treatment refractory hormone receptor positive (HR+) metastatic breast cancer (MBC). The tolerability and activity of abemaciclib + fulvestrant (F) supported Phase 3 evaluation. Methods: MONARCH 2 is a double-blind Phase 3 trial of abemaciclib + F vs placebo (P) + F in women with HR+/HER2- advanced breast cancer. Women who progressed on (neo)adjuvant endocrine therapy (ET), ≤12 months from end of adjuvant ET, or on first line ET for MBC and who had not received chemotherapy for metastatic disease were eligible. Pts were randomized 2:1 to receive abemaciclib at 150 mg Q12H (or 200 mg prior to amendment) or P plus F (500 mg, per label) and stratified by metastatic site (visceral, bone only, or other) and resistance to prior ET (primary vs secondary). Pre/perimenopausal pts received a gonadotropin-releasing hormone agonist. The primary objective was investigator-assessed progression-free survival (PFS). Secondary endpoints included objective response rate (ORR) and other efficacy and safety endpoints. Assuming a hazard ratio (HR) of 0.703 in favor of abemaciclib + F, 378 events were needed for 90% power at one sided α=.025. Results: 669 pts were randomized to abemaciclib + F (N=446) and to P + F (N=223). 56% of pts had visceral disease, 72% had measurable disease, 25% had primary ET resistance, and 82% were postmenopausal. In the ITT population 379 PFS events were observed with a median PFS of 16.4 m for abemaciclib + F and 9.3 m for P + F (HR: 0.553; 95% CI: 0.449, 0.681, P<.0000001 by log-rank test). In pts with measurable disease, the ORR was 48.1% (3.5% complete response [CR]) for abemaciclib + F and 21.3% (0% CR) for P + F. The most frequent treatment emergent adverse events for abemaciclib + F vs P + F were diarrhea (86.4% vs 24.7%), neutropenia (46.0% vs 4.0%), nausea (45.1% vs 22.9%), and fatigue (39.9% vs 26.9%). Conclusions: Abemaciclib + fulvestrant was an effective treatment in patients with HR+/HER2- advanced breast cancer who progressed on endocrine therapy with significantly improved PFS and ORR. Clinical trial information: NCT02107703.
Overall survival results from the randomized phase II study of palbociclib (P) in combination with letrozole (L) vs letrozole alone for frontline treatment of ER+/HER2– advanced breast cancer (PALOMA-1; TRIO-18).
Authors: Finn Richard S. , Crown John , Lang Istvan , Boer Katalin , Bondarenko Igor , Kulyk Sergey O. , Ettl Johannes , Patel Ravindranath , Pinter Tamas , Schmidt Marcus , Shparyk Yaroslav V. , Thummala Anu , Voytko Nataliya L. , Fowst Camilla , Huang Xin , Kim Sindy , Slamon Dennis J.
Published: September 2018

1001

Background: Preclinical data identified a synergistic role for P and hormone blockade in blocking growth of ER+ breast cancer (BC) cell lines. PALOMA-1 was an open-label phase II trial comparing progression-free survival (PFS) in patients (pts) with advanced ER+/HER2– BC treated with P+L or L alone. Median PFS increased with addition of P to L to 20.2 mos (vs 10.2 mos with L alone; HR = 0.488), with an acceptable safety profile, leading to accelerated approval by the US FDA. These results were confirmed in the phase 3 PALOMA-2 trial. At the time of the final PFS analysis, overall survival (OS) data were immature with only 61 events in both arms and a median follow-up of < 30 mos with a trend in favor of P+L vs L (37.5 vs 33.3 mos; HR = 0.813; P= 0.211). Here we present final OS results. Methods: PALOMA-1 was a 2-part study evaluating P+L in ER+/HER2– advanced BC. Part 1 enrolled postmenopausal pts with this subtype using only ER+/HER2– while Part 2 enrolled pts of this subtype additionally screened for CCND1 amplification and/or loss of p16. The primary endpoint was investigator-assessed PFS. Secondary endpoints included objective response rate, OS, safety, and correlative biomarker studies. A total of 165 pts were randomized; 66 in Part 1 and 99 in Part 2. Baseline characteristics were balanced between treatment arms. In both parts, pts were randomized 1:1 to receive P+L or L alone. OS data were collected as well as post-study therapy. Results: As of Dec 2016, there were 116 OS events. Median OS was 37.5 mos (95% CI: 31.4, 47.8) with P+L vs 34.5 mos (95% CI: 27.4, 42.6) for L (HR = 0.897 [95% CI: 0.623, 1.294]; P= 0.281). Median OS was 37.5 vs 33.3 mos (HR = 0.837; P= 0.280) for Part 1 and 35.1 vs 35.7 mos (HR = 0.935; P= 0.388) for Part 2. 78.6% of pts in the P+L arm received post-study systemic therapy vs 86.4% in the L arm. More pts in the L arm received ≥3 lines of therapy (37% vs 18%). Further subgroup analyses and details on post-study therapies will be presented. Conclusions: In PALOMA-1, P+L provided a statistically non-significant trend towards an improvement in OS. Survival data from the phase III, PALOMA-2 study is awaited. Sponsor: Pfizer; Clinical trial information: NCT00721409.
New-onset congestive heart failure (CHF) and cardiovascular disease (CVD) in older colorectal cancer (CRC) survivors: A population-based study.
Authors: Kenzik Kelly , Balentine Courtney , Bhatia Smita , Williams Grant Richard
Published: September 2018

10011

Background: CRC is primarily a disease of the elderly. The high burden of pre-existing comorbidities alone or in concert with cancer treatment place the older patients with CRC at increased risk of new-onset morbidities, specifically, CVD and CHF. However, the magnitude of risk of new-onset morbidity, and its association with pre-existing comorbidities or treatment remain unknown. Methods: Using SEER-Medicare data, we evaluated individuals diagnosed with incident stage I-III CRC at age ≥66y between 1/1/2000 and 12/31/2011 who had survived ≥2y after diagnosis (n = 57,256; 77% with colon cancer). We compared these to an age, sex-, and race-frequency matched comparison group of non-cancer Medicare patients (n = 104,731). We evaluated new-onset CHF and CVD using competing risk cumulative incidence functions and multivariable Cox regression models. Results: The median age at diagnosis was 77y (66-106y); 45% males; and 85% non-Hispanic white. Median follow-up was 8y (2-14y) from diagnosis of CRC. Treatment included surgery for 99%, chemotherapy for 31%, and radiation for 12%. New-onset morbidity: The 10y cumulative incidence of new-onset CHF and CVD were 43.6% and 58.9%, respectively. After controlling for pre-cancer comorbidities, CRC survivors were at increased risk of new-onset CHF (HR 1.29) and CVD (HR 1.74) (all p < 0.001) compared to controls. Patients receiving radiation (HR 1.29) or 5-FU+oxaliplatin (HR 1.09) were at increased risk of CVD compared to those without those therapies (p < 0.001). Pre-existing diabetes (HR 1.16) and CHF (HR 1.21) independently increased the risk of CVD (p < 0.001). While 5FU+oxaliplatin did not increase the risk of CHF independently (HR 0.97), diabetic patients treated with 5-FU+oxaliplatin were at 1.71-fold increased risk of developing CHF (p < 0.001) when compared with those without pre-existing diabetes. Conclusions: Older CRC survivors are at increased of developing CHF and CVD. Monitoring survivors with a history of exposure to 5FU+oxaliplatin or radiation, and improving management of pre-existing comorbidities may reduce the burden of long-term morbidity for older CRC survivors.
A phase II trial of the CDK4/6 inhibitor palbociclib (P) as single agent or in combination with the same endocrine therapy (ET) received prior to disease progression, in patients (pts) with hormone receptor positive (HR+) HER2 negative (HER2−) metastatic breast cancer (mBC) (TREnd trial).
Authors: Malorni Luca , Curigliano Giuseppe , Minisini Alessandro Marco , Cinieri Saverio , Tondini Carlo , Arpino Grazia , Pavesi Lorenzo , Martignetti Angelo , Criscitiello Carmen , Puglisi Fabio , Pestrin Marta , Sanna Giuseppina , Moretti Erica , Risi Emanuela , Biagioni Chiara , Boni Luca , Baldari Daniela , Buyse Marc E. , Biganzoli Laura , Di Leo Angelo
Published: September 2018

1002

Background: P is approved for treatment of HR+/HER2− mBC combined with ET. There is paucity of clinical data of single-agent P in ET resistant pts. Pre-clinical data suggest P may partially reverse endocrine resistance, though this is yet to be tested in pts. Methods: This Phase II, open-label, multicenter study enrolled post-menopausal pts with HR+ HER2− mBC who progressed on 1 or 2 prior ETs. Pts were randomized to P (125 mg/d 3 w on/1 w off) alone or to continue their current ET (aromatase inhibitor or fulvestrant) in combination with P (same schedule as P arm). The primary endpoint was clinical benefit rate (CBR) [complete response (CR), partial response (PR) and stable disease (SD) for > 6 months (mo)]. Secondary endpoints were adverse events (AE) and additional measures of efficacy. A two-stage optimal design assessed treatment activity in each arm assuming activity as CB≥40% (α and β = 10%). Exploratory comparisons were planned for safety and efficacy endpoints. Results: 115 pts were enrolled (ITT population) 58 in the P arm and 57 in the P+ET arm. In both arms, 67% of pts had the study treatment as second line ET, 33% as third line, and about 1/3 of pts also received 1 prior chemotherapy for mBC. CBR was similar in both arms: 54% (95% CI 42 - 67%) with P+ET, and 60% (95% CI 48 -73%) with P alone. Median duration of CB was longer with P+ET (11.5 mo; 95% CI 8.6 – 17.8) than with P (6 mo; 95% CI 3.9 - 9.9) (HR 0.31, 95% CI 0.1 - 0.7, p-value 0.001, exploratory). Objective response rate (ORR; CR, PR) was 11% (95% CI 3 - 19%) and 7% (95% CI 0.4 -13%) with P+ET and P, respectively. PFS was 10.8 mo (95% CI 5.6 - 12.7) with P+ET and 6.5 mo (95% CI 5.4 - 8.5) with P alone (HR 0.69, 95% CI 0.4 - 1.1, p-value 0.13, exploratory). AEs were in line with previous data. Conclusions: Single agent P has clinical activity in ET pre-treated HR+/HER2– mBC pts. The observed increase in PFS and duration of CB with P+ET may suggest that P could reverse resistance to the prior line of ET. Translational studies are ongoing to explore potential biomarkers in this setting. Clinical trial information: NCT02549430.
Pre-planned safety analysis of NORDIC 9: A randomized trial comparing full dose monotherapy (S-1) with reduced dose combination therapy (S-1/oxaliplatin) in older chemo-naive patients with metastatic colorectal cancer (mCRC).
Authors: Winther Stine Brændegaard , Osterlund Pia J. , Berglund Ake , Glimelius Bengt , Qvortrup Camilla , Sorbye Halfdan , Pfeiffer Per
Published: September 2018

10032

Background: More than half of the patients (pts) diagnosed with mCRC are older, but they are underrepresented in clinical trials. Data about the best treatment strategy in pts who are not candidates for standard full-dose combination therapy is scanty. Here we present a preplanned safety analysis in the NORDIC 9 trial. Methods: NORDIC 9 explores treatment of older mCRC pts (≥70 years) who are not candidates for full-dose combination therapy. Pts receive full dose monotherapy (Arm A: S-1 30 mg/m2 po bid day 1-14 q3w, followed by irinotecan upon progression or reduced dose (80%) combination therapy (Arm B: S-1 20 mg/m2 po bid day 1-14 + oxaliplatin 100 mg/m2 iv day 1 q3w, followed by reduced dose S-1 + irinotecan q3w). Bevacizumab (7.5 mg/kg iv day 1) may be added at the discretion of the treating clinician. Geriatric screening tools (eg G-8 and VES-13) and quality-of-life are evaluated at baseline. Blood samples and tumor tissue are prospectively collected. Primary endpoint is PFS. Secondary endpoints are correlations between the geriatric screening and safety but also efficacy. Results: The safety analysis was performed when 50 pts had received 3 cycles. 12 pts received bevacizumab. Median age was 79 (range 70-88) years, 26 pts were male, performance status was 0 (43%), 1 (38%) or 2 (19%). Five (10%) pts discontinued therapy after only 1 cycle due to toxicity (n = 2) or PD/clinical deterioration (n = 3); 45 pts (90%) continued therapy beyond 3 cycles. Pts receiving only 1 cycle had numerically a worse G-8 and VES-13 score. Grade 3-4 non-hematological toxicity was fatigue (6%), diarrhea (10%), nausea (4%) and vomiting (6%), and was experienced by 10 pts, 6 of them received ≥3 cycles of treatment. There was no hand-foot-syndrome, cardiac or hematological grade 3-4 toxicity. Dose intensity for S-1 was 0.98 (0.7-1.0) (arm A) and 0.93 (0.6-1.0) (Arm B), respectively, and for oxaliplatin 0.99 (0.4-1.0). Conclusions: The safety committee recommends to continue the trial without dose adjustments according to the original design. February 2017, 118 of planned 150 pts had been included. Clinical trial information: EudraCT no 2014-000394-39.
A phase II trial of older adults with metastatic breast cancer (MBC) receiving nab-paclitaxel: Melding the fields of geriatrics and oncology.
Authors: Soto Perez De Celis Enrique , Blanchard Suzette , Mortimer Joanne E. , Burhenn Peggy , Yeon Christina Haeyoung , Yuan Yuan , Li Daneng , Katheria Vani , Waisman James Ross , Luu Thehang H. , Somlo George , Noonan Anne M. , Lee Ty , Sudan Nimit , Chung Samuel , Arsenyan Anait , Levi Abrahm , Choi Jennifer , Rubalcava Andrea , Hurria Arti
Published: September 2018

10035

Background: The Institute of Medicine and ASCO identified key research priorities to improve the evidence base of older adults with cancer, including the need for therapeutic phase II trials. Here we present a phase II study of nab-paclitaxel in older patients (pts) with MBC, incorporating geriatric oncology principles in the study design. Methods: Pts age ≥65 years with MBC and 0-1 chemotherapy (CT) lines received nab-paclitaxel (100 mg/m2, 3 wks on, 1 wk off). Pts completed a geriatric assessment (GA) pre-CT including measures of function, comorbidity, cognition, nutrition, and psychosocial status. A CT toxicity (tox) risk score was calculated for each pt (Hurria et al. JCO 2011 and 2016). Relationships between tolerability (no. courses, hospitalizations, dose reductions, and grade (G) ≥3 tox attributed to CT) and risk score were assessed using generalized linear models, Student’s t tests, and Fisher’s exact test. Response rate (RR) and progression free survival (PFS) were evaluated. Results: 40 pts (mean age 73 [65-87]) were accrued from 06/12 to 01/16. Median no. of cycles was 6 [0-33], RR was 35% (95% CI 21-52%) and PFS was 6.5 months (95% CI 5.5-NR). 58% (n = 23) of pts had G ≥ 3 tox and 30% (n = 12) were hospitalized due to CT. G 2/3 neuropathy and G 3/4 neutropenia occurred in 10% of pts (n = 4), with no cases of febrile neutropenia. Based on the CT tox risk score, 53% (n = 21), 38% (n = 15), and 10% (n = 4) were low, intermediate, and high risk. As a continuous variable, doubling in the risk score was associated with a reduction in courses completed of 4.5 (se = 1.4, p = 0.003). Lower mean log2 risk scores were found in pts that did not require hospitalization (diff = -0.59, 95% CI -1.00, -0.18; p = 0.007), or did not have a dose reduction (diff = -0.46, 95% CI -0.85, -0.06; p = 0.02). G ≥ 3 tox was found in 38% of low, 73% of intermediate and 100% of high risk pts, with combined intermediate/high risk pts experiencing significantly more G ≥ 3 tox (OR 5.8, 95% CI 1.3-33.1; p = 0.01). Conclusions: This phase II trial of older pts with MBC receiving nab-paclitaxel incorporated geriatric principles in an oncology trial. Incorporating the GA and CT tox risk score can help weigh the risks and benefits of therapy in older adults. Clinical trial information: NCT01463072.
Influence of patient characteristics on provider surveillance for colorectal cancer.
Authors: Brell Joanna M. , Bruno Debora S. , Lewis Steven A , Thornton John Daryl
Published: September 2018

10071

Background: The majority of colorectal cancer (CRC) patients present with resectable disease and benefit from future resection of second primary CRC, local recurrence, and oligometastases. Therefore, in addition to colonoscopy one year after diagnosis, American Society of Clinical Oncology (ASCO) offers consensus recommendations to monitor serum CEA and CT scans for early detection. Limited adherence to guidelines has been reported; we explore the impact of specific patient factors related to CRC on provider prescribing in the first year. Methods: At a single urban safety-net hospital, electronic medical records of patients diagnosed with stages I-III CRC from 2002-2014 were reviewed with IRB approval. Chi-square tests determined extent of associations between categorical variables. Two sample t-tests compared means for continuous outcomes across groups. Cut-off for Type 1 error was alpha = 0.05. Due to minimal change in surveillance guidelines, we applied ASCO 2005 recommendations. Results: Records for 357 patients included 52% females and 40% African-Americans. Median age was 63 years, ever tobacco abuse was 69%. BMI > 30 found in 38%, median weight at diagnosis was 79 kg. Incidence of surveillance and associated variables are in the Table. Conclusions: The providers of this young, urban, almost 40% obese population were < 50% compliant with first year colonoscopy and < 60% compliant with CEA tests. Providers did significantly survey patients with co-morbidities, such as higher weight at diagnosis, in this small study. Most patients complied with orders and primary care providers were least compliant (data not shown). The data supports verification in larger study of safety-net hospitals and future comparison regarding influence of new Survivorship Care Plans on guideline adherence. To improve provider compliance, etiology of nonadherence must be addressed. [Table: see text]
Phase 2 study of pembrolizumab (pembro) monotherapy for previously treated metastatic triple-negative breast cancer (mTNBC): KEYNOTE-086 cohort A.
Authors: Adams Sylvia , Schmid Peter , Rugo Hope S. , Winer Eric P. , Loirat Delphine , Awada Ahmad , Cescon David W. , Iwata Hiroji , Campone Mario , Nanda Rita , Hui Rina , Curigliano Giuseppe , Toppmeyer Deborah , O'Shaughnessy Joyce , Loi Sherene , Paluch-Shimon Shani , Card Deborah , Zhao Jing , Karantza Vassiliki , Cortes Javier
Published: September 2018

1008

Background: In KEYNOTE-012, pembro showed durable activity and manageable safety in patients (pts) with PD-L1+ mTNBC. Cohort A of KEYNOTE-086 (NCT02447003) examined the efficacy/safety of pembro in previously treated mTNBC, regardless of PD-L1 expression. Methods: Pts with centrally confirmed mTNBC, ≥1 prior chemotherapy for metastatic disease, and ECOG PS 0-1 had pembro 200 mg Q3W for up to 24 mo; imaging q 9 wk for the first 12 mo, then q 12 wk. Clinically stable pts with PD could remain on pembro until PD confirmed on next assessment. Primary endpoints: ORR (RECIST v1.1, central review) in all pts and pts with PD-L1+ tumors, and safety. Secondary endpoints: DOR, disease control rate (DCR; CR + PR + SD ≥24 wk), PFS, and OS. Planned enrollment was 160 pts; analysis based on data as of Nov 10, 2016. Results: 60% of screened PD-L1-evaluable pts had PD-L1+ tumors (combined positive score ≥1%). Of 170 pts enrolled (100% women; median age 54 y), 44% had ≥3 prior lines of therapy, 51% had elevated LDH, 74% had visceral mets and 62% had PD-L1+ tumors. After a median follow-up of 10.9 mo, 9 (5%) pts remained on pembro. Treatment-related AEs (TRAEs) of any grade and grade 3-4 occurred in 60% and 12% of pts, respectively; 4% discontinued due to TRAEs. There were no deaths due to AE. Overall ORR was 5% regardless of PD-L1 expression (Table). Best overall response was 0.6% CR, 4% PR, 21% SD; not evaluable (3%). DCR was 8% (95% CI 4-13). Median DOR was 6.3 mo (range 1.2+ to 10.3+); 5 (63%) responders w/o PD at data cutoff. Median PFS and OS were 2.0 mo (95% CI 1.9-2.0) and 8.9 mo (95% CI 7.2-11.2), with 6-mo rates of 12% and 69%, respectively. ORR was numerically lower in pts with poor prognostic factors (e.g., high LDH, liver/visceral mets; Table). Conclusions: In KEYNOTE-086 Cohort A, pembro monotherapy showed manageable safety and durable responses in a subset of pts with heavily pretreated mTNBC. Randomized studies of monotherapy and combination therapy are ongoing. Clinical trial information: NCT02447003. [Table: see text]
Phase III study of NEPA, a fixed combination of netupitant and palonosetron, versus an aprepitant regimen for prevention of chemotherapy-induced nausea and vomiting (CINV).
Authors: Zhang Li , Lu Shun , Feng Ji Feng , Dechaphunkul Arunee , Chessari Salvatore , Lanzarotti Corinna , Jordan Karin , Aapro Matti S.
Published: September 2018

10090

Background: Co-administration of multiple antiemetics that inhibit several molecular pathways involved in emesis is required to optimize CINV control in patients receiving highly emetogenic chemotherapy (HEC). NEPA, a novel fixed combination of a highly selective NK1 receptor antagonist (RA), netupitant (300 mg), and palonosetron (PALO 0.50 mg), a pharmacologically distinct 5-HT3RA, has shown superior CINV prevention compared to PALO in cisplatin and AC-based settings. This study is the first head-to-head comparison of NEPA versus an aprepitant (APR)/granisetron (GRAN) regimen, with the primary objective being to demonstrate non-inferiority in preventing CINV. Methods: This randomized, double-blind, parallel group Phase III study conducted in an Asian population was designed to compare efficacy and safety of a single oral dose of NEPA with a 3-day oral APR/GRAN regimen in chemotherapy-naïve patients receiving cisplatin-based HEC. All patients also received oral dexamethasone (DEX) on days 1-4. The primary efficacy endpoint was complete response (CR: no emesis, no rescue medication) during the overall (0-120 h) phase. Non-inferiority was defined as a lower 95% CI greater than the non-inferiority margin set at -10%. Secondary efficacy endpoints included no emesis and no significant nausea (NSN: < 25mm on 100mm VAS). Results: Treatment groups were comparable for the 828 patients analyzed: predominantly male (71%); mean age 54.5 years; ECOG 0-1 (98%); lung cancer (58%). NEPA demonstrated non-inferiority to APR/GRAN for overall CR; no emesis and NSN rates favored NEPA. Most frequent study drug-related adverse events (AEs) for NEPA included constipation (8.0%) and hiccups (2.7%). The type/incidence/severity of AEs were similar for NEPA and APR/GRAN. Conclusions: In this first study comparing NK1RA regimens and 4 days of DEX, NEPA administered only on day 1 was non-inferior to a 3-day oral APR/GRAN regimen in preventing CINV associated with HEC. [Table: see text]
A longitudinal brain fMRI study of chemotherapy-induced peripheral neuropathy in 50 breast cancer patients.
Authors: Kleckner Ian , Aslin Richard , Heckler Charles E. , Janelsins Michelle Christine , Mohile Nimish , Asare Matthew , Cole Calvin , Lin Po-Ju , Mustian Karen Michelle , Rao Vikram , Kesler Shelli
Published: September 2018

10095

Background: Over half of patients receiving taxane, platinum, and vinca alkaloid chemotherapy experience chemotherapy-induced peripheral neuropathy (CIPN), which involves numbness and neuropathic pain in the hands and feet. CIPN has no effective treatments partly because its etiology is poorly understood. We theorize that CIPN symptoms are partly caused by impairment of interoceptive brain circuitry, which processes bodily sensations via the posterior insula and anterior cingulate cortex (ACC). We investigated whether CIPN is associated with altered connectivity in interoceptive brain circuitry. Methods: Fifty women with breast cancer (50±9 years) reported CIPN symptoms (CIPN-20) and underwent resting fMRI one or more times: before surgery, one month after completion of chemotherapy, and one year after chemotherapy. We used an a priori seed-based investigation of connectivity between the posterior insula and ACC. We compared connectivity between 31 patients without CIPN symptoms (≤10 CIPN-20-Sensory), 19 patients with CIPN symptoms ( > 10 CIPN-20-Sensory), and 280 healthy adults (174 women, 19.3 years) from another study. Results: Patients with CIPN symptoms had significantly reduced connectivity between the posterior insula and the ACC compared to patients without CIPN symptoms (p = 0.01, d = 0.73). Connectivity between the posterior insula and the ACC was negative in patients with CIPN symptoms but positive in both healthy adults and patients without CIPN symptoms. Conclusions: CIPN is characterized by reduced connectivity in interoceptive brain circuitry. Interoceptive networks may be a target for the development of therapies directed to prevent or treat CIPN. Future work will assess causal relationships between CIPN symptoms and reduced connectivity.
Elsiglutide in the primary prevention of chemotherapy (CT)-induced diarrhea in patients with colorectal cancer (CRC) receiving 5-fluorouracil (5-FU)-based CT: A multinational, randomized, double-blind, placebo-controlled study.
Authors: Karthaus Meinolf , Fedyanin Mikhail , Bondarenko Igor , Chessari Salvatore , Spezia Riccardo , Giorgino Ruben
Published: September 2018

10101

Background: Diarrhea is a burdensome toxicity of 5-FU-based regimens and may lead to CT dose intensity reduction. We investigated the efficacy of 3 subcutaneous (s.c.) doses of elsiglutide (a GLP-2 analog) vs. placebo and vs. each other, in the primary prevention of CT induced diarrhea in patients (pts) with CRC receiving FOLFOX or FOLFIRI. Methods: Pts were randomized equally to receive placebo or elsiglutide 10, 20, or 40 mg s.c. on days (d)1–4 of the first 2 CT cycles and were followed up in cycle 3 for safety only. Stratification factors were CT regimen and country. Primary endpoint was the proportion of pts with diarrhea of CTC grade ≥2 in cycle 1. Changes in plasma levels of citrulline, a marker of intestinal mass, from baseline to d5 and d14 of each cycle were analyzed. With 480 pts randomized, the study had 85% power to detect a 15% difference vs. placebo for each dose at an alpha level of 0.1, assuming a 20% frequency of diarrhea CTC grade ≥2 in the placebo arm. Results: Treatment groups were comparable for the 484 pts (142 receiving FOLFIRI) who were randomized to receive placebo (n = 123), elsiglutide 10 mg (n = 120), 20 mg (n = 121), or 40 mg (n = 120), respectively. The proportion of pts with diarrhea CTC grade ≥2 was higher with placebo (10%) than with elsiglutide 10 mg (3%), 20 mg (5%) and 40 mg (6%); differences were not statistically significant. A similar pattern was observed in cycle 2. Differences in diarrhea frequency between placebo and elsiglutide groups were pronounced in the FOLFIRI subgroup (cycle 1: 18% with placebo, 6% with 10 mg and 20 mg; 3% with 40 mg elsiglutide). Reduction of citrulline levels was smaller with elsiglutide compared with placebo. The safety profile of all elsiglutide doses was acceptable with few related injection site reactions, mostly at the highest dose. Conclusions: Although a lower frequency of diarrhea CTC grade ≥2 was observed with elsiglutide, this difference was not statistically significant in pts receiving FOLFOX or FOLFIRI for CRC. Interpretation must consider the unexpectedly low reported frequency of diarrhea of grade ≥2, particularly with FOLFOX regimens. Clinical trial information: 2014-000998-39.
A double blind, randomised placebo controlled trial evaluating the effect of a pholyphenolic rich plant based nail bed balm on the severity of chemotherapy-induced onycholysis.
Authors: Thomas Robert J. , Williams Madeleine M A , Mutilib Masoom , Berkovitz Saul , Attia Fawzi , Cauchi Michael , Smith Sarah
Published: September 2018

10103

Background: Nail damage is common amongst patients receiving chemotherapy, especially taxanes, causing pain, distress, disfigurement, infection and restricted daily activities. Cooling the nail beds helps but there has been no published evidence for the effectiveness of nail balms, despite their popular use. We investigated whether a topical nail bed balm containing bioactive polyphenolic rich African salvia officinalis, gaultheria procumbens in a natural base of olea europaea, butyrospermun parkii, cera alba and theobroma cacao protected the nail beds via their reported anti-inflammatory, analgesic, anti-oxidant and anti-microbial properties. Methods: 60 patients (23 male, 37 female) were randomized to apply to their nail bed (tds) the natural balm or a petroleum balm suitably scented for a placebo control. Demographics, type and number of chemotherapy cycles did not differ between the two groups, recruited between Sept 2016-Sept 2017. At baseline and at the end of chemotherapy both patients and physicians measured outcomes of nail health. Patients completed a Dermatology Life Quality questionnaire and a linear severity scale; physician completed a Nail Psoriasis Index (NPSI) and a linear severity scale based on clinical examination and photographs. Differences were analyzed using an unpaired t-test; significance level α = 0.05 at 95% confidence intervals (CI); probability (p). Results: The mean change in nail health outcomes over the course of chemotherapy were: (see table). Conclusions: The polyphenolics rich essential oils and plant-based waxes in this nail bed balm profoundly reduced chemotherapy related nail damage and improved nail related quality of life compared to a plain petroleum based balm. A future evaluation combining nail bed cooling and this natural balm is planned. Clinical trial information: 015-001866-24. [Table: see text]
Next-generation sequencing ordering trends in the cancer trajectory.
Authors: Ma Joseph , Hagmann Chelsea , Dullea Alexandra , Wang Winnie S , Yau Warren , Revta Carolyn , Armstrong Janet M , Roeland Eric
Published: September 2018

10104

Background: Next-generation sequencing (NGS) molecular tumor profiling is increasingly being ordered for advanced cancer patients to evaluate non-traditional therapeutic options. The timing of when NGS is ordered relative to date of diagnosis, palliative care (PC) consultation, and death remains unknown. The primary objective of this study was to examine NGS ordering patterns among cancer patients. Methods: This was a single center, retrospective data analysis in cancer patients at our institution between January 2011 and February 2016. Cancer patients ≥16 yrs of age were identified from a tumor registry and matched to an existing NGS tumor profiling database. Additional data were collected from an electronic medical record and compiled into a single database. Differences in the date of when NGS was ordered compared to date of diagnosis, PC consultation, and/or date of death were determined. A Mann-Whitney rank sum test examined differences in patients where NGS was ordered relative to the date of PC consultation. Logistic regression examined variables possibly associated with PC consultation. Results: Analysis included 1596 (807 women) cancer patients. Mean±SD age was 55.5±15.2 years, 30.8% (n = 492) of patients had metastatic disease, with breast and lung the most common cancers. The difference between date of cancer diagnosis and date of NGS order was 1053.6±1568.5 days (n = 1546). The difference between date of NGS order and date of death was 221.2.4±186.6 days. Two-hundred and fifty-one patients (15.7%) received a PC consultation, of which 82 patients had a NGS order before the PC consultation and 169 patients had a NGS order after the PC consultation. The mean difference in number of days between a NGS order before versus after a PC consultation was 147.3±216.8 vs. 179.8±169.7 days (p < 0.005). Four-hundred and sixty-six (29%) patients have died with 121 receiving a PC consultation. Metastatic disease, but not age and sex, was associated with PC completion (OR 1.7; 95%CI 1.27-2.21). Conclusions: NGS was frequently ordered near the time of death. PC consultations were completed in a minority of patients. NGS ordering in advanced cancer patients may serve as a trigger for PC consultation.
Reducing chronic breast cancer related lymphedema utilizing a program of prospective surveillance with bioimpedance spectroscopy (BIS).
Authors: Whitworth Pat W. , Shah Chirag , Vicini Frank , Cooper Andrea
Published: September 2018

10117

Background: Breast cancer related lymphedema (BCRL) represents a major side effect that can significantly impact quality of life. Current guidelines support prospective surveillance to allow for early diagnosis and treatment of BCRL at a subclinical, reversible stage. This current large, single institution experience evaluated the use of bioimpedance spectroscopy (BIS) to monitor patients for the development and treatment of BCRL. Methods: From April 2010 through Nov 2016, 596 patients (79.6% with high-risk features) were evaluated with BIS.Patients received a pre-operative baseline L-Dex measurement and post-operatively at regular intervals. Elevated L-Dex scores were defined as an increase of ≥10 points above baseline (considered subclinical BCRL). Intervention then consisted of applying an over the counter (OTC) sleeve for 4 weeks followed by re-evaluation. The need for complete decongestive physiotherapy (CDP) represented a surrogate for the development of clinically significant, chronic BCRL. Results: Median follow-up for all patients was 17 months. Seventy-three patients (12%) developed an elevated L-Dex score with axillary lymph node dissection (ALND) (p < 0.001), taxanes (p = 0.008), and (regional nodal irradiation (RNI) (p < 0.001) associated. At last follow-up, only 18 patients (3%) had unresolved clinically significant BCRL requiring CDP. Mastectomy (p = 0.02), ALND (p < 0.001), taxanes (p = 0.05), and RNI (p < 0.001) were associated with requiring CDP. Conclusions: Our results demonstrate that prospective monitoring using BIS, with intervention (using a simple OTC sleeve for 4 weeks) triggered by a ≥10-point L-Dex elevation, resulted in only a 3% rate of chronic, clinically significant BCRL. These results are lower than reported in contemporary studies and validate recent guidelines supporting prospective screening and intervention for BCRL.
FGFR gene amplification and response to endocrine therapy in metastatic hormone receptor positive (HR+) breast cancer.
Authors: Drago Joshua Z. , Niemierko Andrzej , Spring Laura , Moy Beverly , Juric Dejan , Isakoff Steven J. , Iafrate A. John , Ellisen Leif W. , Bardia Aditya
Published: September 2018

1013

Background: Amplification in Fibroblast Growth Factor Receptor (FGFR) genes occurs in 10% of breast cancers, is associated with poor prognosis, and appears to drive resistance to endocrine therapies in vitro. However, the role of FGFR in modulating the clinical response to endocrine therapies is unclear, and could have important implications given that FGFR is a potential therapeutic target. This study aims to evaluate the association between FGFR amplification and clinical response to endocrine therapy in HR+ metastatic breast cancer (MBC). Methods: Primary or metastatic tumor specimens from patients with HR+/HER2 negative MBC underwent dual-color fluorescence in situ hybridization (FISH) of the FGFR1 locus on chromosome 8p. FISH ratios of ≥2 were considered positive for gene amplification (FGFR+). Time to progression (TTP) on first line endocrine therapy was evaluated in FGFR+ versus wild type (WT) patients using actuarial analysis. Results: Between 2012 and 2016, we identified 95 patients with HR+ MBC who underwent FGFR FISH testing. Of these, 24 (25.3%) were FGFR+. FGFR+ and WT patients did not differ in being postmenopausal at initial breast cancer diagnosis (28.6% vs. 31.7%; p = 1.0), having de-novo MBC (16.7% vs. 21.1%; p = 0.773), having received adjuvant chemotherapy (75% vs. 76.8%; p = 1.0) or having received adjuvant endocrine therapy (90% vs. 91.1%; p = 1.0). However, FGFR+ patients tended to be younger than WT patients (54.3 vs. 59.3 years; p = 0.045), and more likely to have PR-negative MBC (50.0% vs. 19.1%; p = 0.011). While there was no difference in TTP on first-line chemotherapy in FGFR+ vs. WT patients (5.0 vs. 6.2 months; p = 0.8), FGFR+ patients had a shorter median TTP on first-line endocrine therapy than WT (8.5 vs. 10.8 months; p = 0.047). These results were similar when stratified by presence of de-novo metastatic disease. Conclusions: In patients with HR+ MBC, FGFR gene amplification is associated with shorter time to progression on first line endocrine therapy. Further studies are needed to confirm these findings, and to investigate potential strategies for endocrine therapy and FGFR-directed combinatorial therapy in FGFR+ breast cancer.