bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.