bluuebunny/crossref_metadata_2025 huggingface dataset:
The ability of avitinib to penetrate the blood brain barrier and its control of intra-/extra- cranial disease in patients of non-small cell lung cancer (NSCLC) harboring EGFR T790M mutation.
Authors: Wang Hanping , Zhang Li , Zheng Xin , Zhang Xiaotong , Si Xiaoyan , Wang Mengzhao
Published: September 2018

e20613

Background: Avitinib is an oral, potent, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor selective for T790M resistance mutations. We report the safety, the intracranial/extracranial efficacy, and the blood brain barrier (BBB) penetration rate of Avitinib in non-small cell lung cancer(NSCLC) patients with EGFR T790m mutation. The data come from Peking Union Medical College hospital-a single center of the Phase I, open-label, multicenter study (NCT02330367). Methods: NSCLC Patients with acquired EGFR T790m (+) were enrolled. Patients were orally administered with dose escalating from 150 mg to 300 mg twice daily for 28-continuous-day cycles until disease progression. Blood (2mL) and cerebrospinal fluid (CSF) samples (2ml) were collected for concentration analysis on day 29 in available patients with brain metastases (BM). Tumor response was assessed on day 29 and then every 8 weeks. Results: Sixteen patients were included. Nine patients had asymptomatic BM. The most frequent adverse events were the elevated hepatic transaminases (10/16, 62.5%) and diarrhea (5/16, 31.3%), Most were mild and reversible. 9 Patients (56.3%) achieved Partial Response (PR), 6 (37.5%) achieved Stable Disease (SD). Median Progress Free Survival (PFS) was 253 days (95%CI: 154.8-339.2). Of the 8 evaluable BM patients, intracranial PFS were shorter than extracranial in only two patients. The blood and CSF analysis of 6 BM patients showed the BBB penetration rate were 0.046%-0.146% (Table). Conclusions: Avitinib is well tolerated and efficacious in EGFR T790m(+) NSCLC patients. Its concentration in CSF is low, and the penetrability of BBB is weak. But it still showed a good control of BM. Further studies are proceeding. Clinical trial information: NCT02330367. [Table: see text]
Distribution and pathogenicity of nsSNPs in receptor tyrosine kinases (RTKs) in non-small cell lung cancer (NSCLC) patients (pts).
Authors: Vanderwalde Ari M. , Stein Matthew K , Morris Lindsay Kaye , Sareen Srishti , Karri Saradasri , Patel Kruti , Sullivan Jennifer , Schwartzberg Lee Steven , Martin Michael Gary
Published: September 2018

e20618

Background: Non-synonymous SNPs (nsSNPs) in RTKs can alter kinase activity and are not exclusive to the tyrosine kinase domain (TKD). In NSCLC, EGFR lesions were previously identified using TKD-limited tests; however, next-generation sequencing (NGS) enables the entire protein sequence of many RTKs to be interrogated. Methods: We analyzed all nsSNPs in 28 RTKs in lung cancer pts who received tumor profiling with Caris NGS from 2013-2015. Mutations were classified by location including the TKD, extracellular domain (ECD), transmembrane domain (TM), juxtamembrane domain (JM), and carboxy-terminal (CT) regions. nsSNPs underwent in silico analysis using PolyPhen-2 (Harvard) to predict pathogenicity. Results: 167 pts (156 NSCLC, 11 SC) were identified with a median age 65 (range 26-85); 51% male; 65% white, 31% black; 77% ≥20 pack-years (py), 11% non-smokers; 52% samples tested were metastases. NSCLC pts were 63% adenocarcinoma, 22%, squamous, 8% large-cell; 81% stage IV, 14% III; 17 were EGFR+, 6 BRAF+, 3 HER2+, 3 ROS1 rearranged and 1 MET exon 14. A total 300 nsSNPs (286 NSCLC, 14 SC) were found in 28 RTKs, excluding EGFR. 123/156 NSCLC pts (79%) and 9/11 SC (82%) had ≥1 RTK lesion with median 2 (range 0-8); 143/300 (48%) nsSNPs were predicted-damaging (pnsSNP) by in silico and 89 pts (53%) had ≥1 pnsSNP (median 1; range 0-5). 28/28 RTKs had ≥3 mutations, with median 11 (range 3-23), and 26/28 contained ≥1 pnsSNP (median 5; range 0-14). RTKs in NSCLC with the most frequent nsSNPs were EPHA3 (14/23 variants were pnsSNP), EPHA5 (11/17), EPHB1 (10/11), RET (9/11), ERBB4 (8/12), ALK (7/16), NTRK3 (7/15), ROS1 (6/22) and FLT1 (6/15). 6/14 lesions in SC pts were pnsSNPs in ERBB3, ERBB4, FGFR1, FLT1, RET and ROS1. nsSNPs were found along RTKs: 57% were ECD (72/172 pnsSNP), 26% TKD (47/77), 10% CT (14/29), 6% JM (8/18) and 1% TM (2/4). 6/6 SC pnsSNPs were ECD. 67% BRAF+ and ROS1-rearranged, 59% EGFR+, 33% HER2+ and 0/1 MET exon 14 pts had ≥1 pnsSNP. Conclusions: Nearly 80% NSCLC and SC pts had ≥1 nsSNP in 28 RTKs, excluding EGFR, with 48% pnsSNPs by in silico analysis. As > 70% nsSNPs were extra-TKD lesions, further characterization is needed to identify kinase-effecting variants and their potential clinical significance.
Incidence and impact of thromboembolic events in lung cancer patients treated with nivolumab.
Authors: Hegde Aparna Madhukeshwar , Stroud Chipman Robert Geoffrey , Cherry Cynthia R. , Yogarajah Meera , Cherukuri Sulochana Devi , Walker Paul R.
Published: September 2018

e20624

Background: Lung cancer has one of the highest incidences of thromboembolic events (TEE) ranging from 8.4 to13.2%. Cisplatin-based chemotherapy in lung cancer is a well-established risk factor for TEE (11.8%). The incidence of TEE in lung cancer patients (pts) treated with nivolumab (nivo) is unclear. The objective of this study was to evaluate the incidence of TEE, risk factors and its impact on overall survival in lung cancer pts treated with nivo. Methods: This was a retrospective cohort study that included all lung cancer pts treated with nivo from April 2015 to October 2016 at our institution. Medical records were reviewed for incidence, timing, CTCAE grade, type and site of TEE, risk factors and patient demographics. Cox proportional hazard model was used to identify independent predictive factors for TEE. Risk factors with p <0.15 in univariate analysis were included in multivariate model using a stepwise approach. Kaplan-Meier method was used to estimate overall survival (OS). Results: The cumulative incidence (CI) of TEE over a median follow up of 10.8 months after starting nivo was 18.4% (14/76 pts). Of the 14 pts who had TEE, 8 had deep vein thrombosis (DVT), 7 had pulmonary embolism (PE), 1 had concurrent DVT/PE and 2 had arterial thrombosis (AT). 28.6% (4/14) of pts experienced recurrent TEE resulting in 18 total episodes. Median time to TEE after starting nivo was 2.9 months (95% CI 1.9 - 8.4). Gender was the only covariate included in multivariate analysis that showed a significant association with TEE (Female vs Male HR 3.1, 95% CI 1.02 – 9.5, p= 0.045). At a median follow up of 31.8 months since diagnosis of lung cancer, pts who had TEE before receiving nivo had worse OS. TEE occurring after nivo had no impact on OS. Conclusions: The CI of TEE is significantly high at 18.4% in lung cancer pts treated with nivo. However, it had no impact on OS. Further studies are needed to determine the role of prophylactic anticoagulation in this high-risk population. [Table: see text]
Detecting T790M mutation of tissue and plasma ctDNA samples by ARMS in EGFR-mutant NSCLC patients after disease progression.
Authors: Wu Ya-Lan , Tong Rui-Zhan , Zhang Yan , Hu Bin-Bin , Zhen Ke , Zhao Qian , Zhou Xiao-Juan , Ding Zhen-Yu , Peng Feng , Gong You-Ling , Xu Yong , Wang Jin , Ren Li , Liu Yong-Mei , Lu You
Published: September 2018

e20625

Background: T790M mutation is the most common mechanism of acquired EGFR TKI resistance. The use of T790M-targeted EGFR TKIs needs re-biopsy to confirm the existence of sensitive mutation. People wonder whether blood can replace tissue to diagnose acquired T790M mutation. Methods: We performed a prospective study in our institution (West China Hospital, Chengdu, China) between 2014 and 2016. Patients were eligible if they have advanced EGFR-mutant NSCLC, clinical resistance to EGFR TKIs, and were undergoing a re-biopsy for EGFR genotyping as part of their routine clinical care. We used ARMS to sequence EGFR of tissue and blood sample. Blood collection was performed within 2 weeks of the repeat biopsy. Measurement of diagnostic concordance among two different methods was done using cohen’s kappa, and the McNemar test used to judge significance. All statistical analysis was performed with the use of SPSS 20.0. Results: Forty-five patients were enrolled in this study. Thirty-eight patients received tissue test, thirty-one patients received plasma ctDNA test, and twenty-four patients received both tissue and plasma ctDNA tests. 26/38 (38.4%) reported positive T790M mutation by tissue test, and 13/31 (41.9%) by plasma ctDNA test. In 24 patients received both tissue and plasma ctDNA tests, 10/24 (41.7%) were concordant for T790M mutation status (κ = 0.006, p = 0.013). The positive rate of T790M mutation is 70.8% by tissue test, and 37.5% by plasma ctDNA test. In 17 patients reported positive T790M mutation by tissue test, 7/17 (41.2%) also reported positive T790M mutation by plasma ctDNA test, and 3 of the 7 positive ctDNA tests (42.9%) reported weakly positive T790M mutation. In the other 7 patients reported negative T790M mutation by tissue test, 2/7 (28.6%) reported positive T790M mutation by plasma ctDNA test. Conclusions: The positive rate of ARMS in our study is high than that of some reported new technologies. The level of plasma ctDNA was reported to relate to prognosis. Hence, plasma ctDNA cannot fully replace tissue to diagnose acquired T790M mutation after disease progression. It is important and significant to develop new technology to improve the safety of tissue biopsy.
Apatinib monotherapy for advanced non-small cell lung cancer after the failure of chemotherapy or other targeted therapy.
Authors: Wang Si-Yu , Liu Zui , Ou Wei , Li Ning , Wu Hui-qi , Mao Xiao-Yong , Yuan Cheng
Published: September 2018

e20626

Background: Apatinib, a small-molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), has been proved to be effective and safe in treating patients with advanced gastric cancer who failed to second-line chemotherapy. As the VEGFR-2 targeted therapy has made encouraging progress in the treatment of a broad range of malignancies, we aimed to explore the efficacy and safety of apatinib in treatment of advanced non-small cell lung cancer after the failure of chemotherapy or other targeted therapy. Methods: In this open-label single-arm, phase II study, patients were treated with apatinib alone in daily dose of 250 mg, po, in the second- or third-line setting. The primary endpoint was progression-free-survival (PFS) and the tumor response was determined according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Results: From January 28, 2016 to December 31, 2016, 33 patients were enrolled, including 9 patients with squamous carcinoma and 24 patients with adenocarcinoma. Fourteen patients were detected as EGFR mutations and all the cases have no anaplastic lymphoma kinase (ALK) fusion gene. The median progression free survival (mPFS) of the whole group was 4.0 (95% confidence interval [CI], 0-8.2) months, while the mPFS of adenocarcinoma was 4.0 (95% CI, 2.1-5.9) months and the mPFS of squamous carcinoma was 5.5 (95% CI, 0-13.9) months (P = 0.245). Among the 33 patients, partial response was noted in 3 patients (9.09 %) and stable disease in 14 (42.42%). The disease control rate (DCR) was 51.52%. The common side effects of apatinib were hypertension, hand-foot syndrome and proteinuria, which accounted for 33.33%, 24.24%, and 15.15%, and no grade 3/4 adverse reactions occurred. The toxicity of apatinib was controllable and tolerable. Conclusions: Apatinib appears to be effective and safe for advanced non-small cell lung cancer after the failure of chemotherapy or other targeted therapy. Prospective studies are needed for further investigation.
In vivo effect of the parasite derived peptide GK-1, anti-PD-L1 and GK-1/anti-PD-L1 combination in experimental melanoma. Potential novel treatment pathways.
Authors: Vera Aguilera Jesus , Perez-Torres Armando , Vera Aguilera Carlos , Block Matthew Stephen , Duma Narjust , Ventolini Gary , Martinez-Zaguilan Raul , Sennoune Souad R.
Published: September 2018

e21038

Background: Several studies of advanced melanoma patients suggest that combining therapies that target tumor mechanisms of immune evasion with activation of normal immune cell functionality may provide optimal benefits for patients. The synthetic parasite derived GK1 peptide in combination with anti-PD-L1 showed significant longer survival (34 days) compared to GK1 or Anti-PD-L1 alone (23-27 days) in a murine melanoma model (p < 0.05). This means an increase survival increased in 47.82% in the mice treated with GK-1 + anti-PD-L1, 21.7% treated with GK-1, and 6.08% treated with anti-PD-L1. Methods: To elucidate the potential mechanism by which this combination treatment exerts its anti-melanoma effects, C57BL/6 mice were injected with B16-F10-luc2 cells and separated according to treatments in four groups: control, GK-1, anti-PD-L1 and GK-1/anti-PDL-1.Blood samples were collected at day 0, 14, and at euthanization or end of the experiment and monitored for serum cytokines using mice-specific V-PLEX Pro-inflammatory Panel. Results: On day 14, TNF-α levels in the Anti-PD-L1 and GK-1 therapy group was significantly lower compared to control mice. At sacrifice, the combined treatment group demonstrated significant decrease cytokine production in IL-6 and IL-10. Conclusions: The decreased cytokine levels observed in the GK-1/anti-PD-L1 group may explain the significant improved survival. GK-1 is a Th1 response inductor both in vitro and in vivo as it increases IFN-γ, IL-2 but not IL-4 and IL-10. It is noteworthy that when PD-L1 signaling is reduced in T cells these cells proliferate extensively in vitro and produce increased levels of IFN-γ and IL-17, suggesting an enhanced pro-inflammatory phenotype. It has been established that cytokines of Th2 response such as IL-4 and IL-5 and IL-6, have tumor-promoting activity. The anti-melanoma effect of the GK-1/anti-PD-L1 combination observed in the present study could be mediated by decreasing the pro-tumor Th2 response. These results provide novel alternative pathways and potential targets to enhance the clinical effect of the PD-1/PD-L1 blockade pathway.
Retrospective review of metastatic uveal melanoma (mUM) at NYU Perlmutter Cancer Center (NYU-PCC).
Authors: Kavecansky Juraj , Finger Paul , Wilson Melissa , Madden Kathleen M. , Kannan Rajni , Pavlick Anna C.
Published: September 2018

e21040

Background: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, despite its rare incidence of 5 per 1,000,000. UM metastasis (mets) occurs in approximately 50% of patients (pts). The published median survival from the time of mets is only 6 to 12 months (mos). To date there is no curative therapy for pts with mUM. Methods: This is a retrospective review of pts evaluated at NYU-PCC with UM between January 1, 2011 and December 31, 2016. Data collected include: ophthalmic treatment, time from ophthalmic diagnosis, systemic metastatic sites, genetic mutations (muts), systemic treatment and survival. Results: During this 5-year interval, 100 UM pts were referred to NYU-PCC. 58 pts were diagnosed with high-risk primary T3/T4 sized tumors and remained disease-free during this period. For the remaining 42 pts that developed mUM, primary ophthalmic treatments included: 12 enucleations, 27 brachytherapy and 3 received none since they had synchronous UM and mUM. Therapy for mUM included liver-directed therapy (LDT) such as TACE, 90Y brachytherapy, or radiofrequency ablation; or systemic therapy. These mUM pts had a median survival of 17 mos. 20 mUM pts are male; 22 pts are female; Ages: 33-96; 24 deceased and 18 alive. Of the latter, 5 are NED and 13 are alive with disease on treatment. 24 deceased mUM pts treated initially with LDT lived on average 14 mos longer than those treated with any systemic therapy alone; pts with LDT had a median survival of 24 mos, compared to 10 mos for those treated only with systemic therapy (p = 0.0075). There was no correlation between time of ophthalmic diagnosis and time to onset of mets and survival (R2value 0.00243). Genetic analysis of met tumors was available on 9 pts. 3 of 5 pts with GNA11 muts are alive compared to 1 of 4 pts with GNAQ muts. Conclusions: Pts with mUM treated initially with LDT had significantly longer survival compared to pts treated with systemic therapy alone. Whether longer survival in these pts is an effect of LDT, earlier treatment of mets, or a more indolent disease remains to be determined. Our study demonstrates mUM pts survive an average of 17 mos, which is higher than historically reported. Significance of GNAQ or GNA11 requires further investigation.
BRAF mutation and PD-L1 expression in melanoma: Comparison between multiple PD-L1 IHC clones and BRAF mutation evalutated by FDA-approved kits versus NGS.
Authors: O'Malley Dennis , Sudarsanam Sucha , Chizhevsky Vladislav , Ma Wanlong , Jiang Shiping , Chen Wayne , Funari Vincent Anthony , Agersborg Sally , Albitar Maher
Published: September 2018

e21050

Background: BRAF mutation and PD-L1 expression appear independent in melanoma. We have established that PD-L1 clones 22C3 and 28.8 show almost identical results. In this study we correlated between BRAF mutation and PD-L1 expression as detected by 22C3/28.8 and SP142 in melanoma clinical samples. Methods: Melanoma samples were tested for PD-L1 expression and BRAF mutation. IHC testing for PD-L1 22C3 or 28.8 were tested using FDA-approved kits as recommended. Testing with SP142 (Spring Biosciences; LDT) was performed using standard techniques. BRAF testing in combination with SP142 PD-L1 testing was performed using next generation sequencing covering exons 11 and 15. Samples tested with 22C3 and 28.8 clones were tested using FDA-cleared BRAF kits (Cobas, Therascreen) testing V600 only. Results: 68 samples were tested for PD-L1 expression with clone 22C3, 67 with 28.8, and 56 with SP142. There was no overall statistical difference between the three clones in PD-L1 expression (P = 0.41). For combined 22C3 and 28.8, 61 of 135 cases (45%) had PD-L1 expression and 31 (23%) had BRAF mutation detected using FDA kits (V600). There was no statistical correlation between PD-L1 expression and BRAF mutation in this group (P = 0.9) at any cut-off. In cases tested with SP142 clone, BRAF mutation was detected in 31 cases (55%) by NGS, higher than using the FDA kit (P < 0.0001). In V600 mutations by NGS, 14 cases (25%) were positive, similar FDA kits. In SP142 cases, PD-L1 was positive in 45% of cases. There was no correlation between BRAF mutation and PD-L1 using SP142 expression as a continuous variable (P = 0.59) or cut-off points of 5% or 50%. When cut-off of 20% was used, significant inverse correlation with BRAF mutation (P = 0.004) was identified and was maintained if V600 codon only was evaluated. Conclusions: There is no correlation between BRAF mutation and PD-L1 expression as detected using clones 22C3 and 28.8. With SP142, a negative correlation between PD-L1 expression and BRAF mutation is identified with a 20% cut-off. The rate of BRAF mutations practically doubles when NGS is used and exons 11 and 15 are included in the testing, in contrast to FDA approved testing.
The prognostic role of preoperative serum lactate dehydrogenase (LDH) in patients with resected advanced melanoma.
Authors: Majithia Neil , Velazquez Manana Ana , Yan Yiyi , Kottschade Lisa A. , Dronca Roxana Stefania , Block Matthew Stephen , Nevala Wendy Kay , Markovic Svetomir
Published: September 2018

e21054

Background: Up to 50% of patients undergoing resection for advanced melanoma experience recurrence. Identification of preoperative prognostic biomarkers is needed to ascertain risk of relapse and guide postoperative management. Lactate dehydrogenase (LDH) represents a strong prognostic factor in unresectable metastatic (stage IV) melanoma, but its relevance in patients with resected stage III or IV disease remains unknown. Methods: We retrospectively analyzed data from patients with stage III and IV melanoma who had undergone complete resection of disease and received follow-up treatment at Mayo Clinic, Rochester between January 1, 2000 and January 31, 2012. Clinical data were collected from electronic records. Survival data were estimated using the Kaplan-Meier method. Associations of preoperative LDH with time to relapse and death were evaluated using Cox proportional hazards regression models and summarized with hazard ratios and 95% confidence intervals. Results: A total of 154 subjects with resectable stage III or IV melanoma were included in the study. Median age at the time of resection was 58; 54 (35.1%) were female. One-hundred sixteen (75.3%) patients were classified as stage III and 38 (24.7%) stage IV. Adjuvant systemic treatment was administered in 75 (48.7%) patients and adjuvant radiation in 32 (20.7%). Median duration of follow-up was 4.0 years. Sixteen (10.3%) patients had preoperative LDH above the upper limit of normal. Each 50-unit increase in LDH was associated with a 15% increased risk of relapse (HR 1.15; p = 0.040) and 23% increased risk of death (HR 1.23; p = 0.001). After adjusting for age, gender, stage, number of sites, adjuvant systemic treatment, and adjuvant radiation, preoperative LDH remained associated with time to death (HR 1.25; p = 0.002). Preoperative LDH greater than the upper limit of normal was associated with increased hazard of death, both with univariate (HR 2.44; p = 0.005) and multivariate (HR 2.17; p = 0.017) analyses. Conclusions: This study supports the role of elevated preoperative LDH as a predictor of inferior outcomes in patients with advanced melanoma. Further study to correlate LDH to outcomes in the era of adjuvant immunotherapy is required.
Patient experiences with avelumab vs chemotherapy for treating merkel cell carcinoma: Results from protocol-specified qualitative research.
Authors: Kaufman Howard , Lambert Jeremy , Barbosa Carla Dias , Guillemin Isabelle , Mahnke Lisa , Bharmal Murtuza
Published: September 2018

e21065

Background: Avelumab is a fully human anti–PD-L1 monoclonal antibody that has shown durable responses and a manageable safety profile in patients (pts) with various tumors, including metastatic Merkel cell carcinoma (mMCC). We report findings from qualitative interviews with mMCC pts about their experiences with avelumab or chemotherapy. Methods: Pts with mMCC who progressed after chemotherapy were enrolled in a registrational, single-arm, multicenter, international phase 2 trial (NCT02155647). Protocol-specified semi-structured phone interviews were conducted at baseline (to document experiences with chemotherapy) and during avelumab treatment at Weeks 13 and 25. Interview transcripts were analyzed qualitatively using a thematic approach. Results: Interviews were conducted with 19 pts at baseline and 10 pts at Weeks 13 and 25. At baseline, most pts (n = 12) reported that chemotherapy was initially successful prior to relapse. At Week 13, pts generally were “optimistic,” but “cautious,” and had “high hopes” regarding avelumab treatment. Pts most frequently reported having no or fewer side effects (n = 6) with avelumab vs prior chemotherapy. At Week 13, fatigue was the most frequently reported impact of avelumab (n = 8); at Week 25, 3 pts still reported fatigue, but 5 “felt less tired” than at Week 13. Most pts (n = 12) had experienced fatigue with chemotherapy; having “less energy” was the most-reported effect (n = 4) when compared with avelumab. Most pts did not report any negative impact of avelumab on everyday lives (n = 7); 3 reported a need “to rest more often after activities.” In contrast, only 6/19 pts reported that chemotherapy had no negative impact or a” very small” negative impact on everyday lives. Eight pts reported feeling “slowed down” or “being limited” in physical capacities during chemotherapy. Eight pts thought that chemotherapy had substantial negative impact on their lives, describing it as “very disruptive,” “debilitating,” or “devastating.” Conclusions: Pts had a more positive experience with avelumab than chemotherapy; it had a minimal detrimental impact on their lives. Clinical trial information: NCT02155647.
Exploring the form of change: A latent growth curve model of distress in oncologic patients undergoing specific cancer-related psychological intervention—A preliminary study.
Authors: Rossi Alessandro , Marconi Maria , Di Lucca Giuseppe , Morena Raffaella , Pogliani Claudia , Parati Maria Chiara , Rossini Chiara , Verusio Claudio
Published: September 2018

e21556

Background: Psychological distress is one of the most important indexes of suffering in oncological patients – due to its severe negative impacts on medical treatments. Thus, the attention to this topic has increased constantly – focusing on the observed outcomes of (psychological) cares. However, very few studies investigated the (latent) pattern ( form) of change in distress within oncological patients receiving psychological intervention. The aim of the study was to test a Latent Growth Curve Model to explore the form of change in distress. Methods: A longitudinal research design was used. Patients ( N= 122, mean age: 68.3, SD= 12.3, 63 female-59 male) were enrolled at the Department of Medical Oncology at Presidio Ospedaliero of Saronno, ASST Valle Olona, Italy, and assessed for the presence of distress with Psychological Distress Inventory (PDI). As clinical routine, all patients received a specific cancer-related psychological intervention (CBT, mainly; mean of sessions: 27.4, SD= 13.5) and were tested at the beginning (T1; α= .88) and at the end of treatment (T2; α= .86) and at timed-balanced follow-up (T3; α= .87). Results: First, longitudinal invariance of measurement was performed to test whether (A) factor structure of PDI and (B) factor loadings of indicators were constant across time. PDI showed metric measurement invariance: Δχ2= 20.4; Δχ2 df= 24; p(Δχ2) = 0.67. Afterward, a LGCM was performed testing different trends of growth (no growth vs. linear vs. free) – controlling for age, number of sessions received, type and localization of tumor. The comparison of growth curves reveal that the linear trends of change had the best model fit to the data: χ2= 4.124, p= .248; RMSEA = .055(.000–.171), p(RMSEA < .05) = .372, CFI = .990, SRMR = .027. Conclusions: These findings highlight that the (latent) linear growth better explain true change of distress – among oncological patients receiving a specific cancer-related psychological intervention. These results outline the possibility to improve the structure of psychological and medical treatments for oncological settings, to reduce psychological suffering and increase quality of life.
Neo-adjuvant chemotherapy and distress in breast cancer patients: The moderating role of generalized self-efficacy.
Authors: Magno Stefano , Carnevale Stefania , Dentale Francesco , Belella Daniela , Linardos Marinella , Masetti Riccardo
Published: September 2018

e21570

Background: Neo-Adjuvant Chemotherapy (NAC) is commonly recommended as a preoperative treatment for patients with locally advanced breast cancers (BC). However, several studies have shown that NAC can increase patients’ distress. A first aim of this study was to evaluate if BC patients treated with NAC show higher levels of distress as compared to patients undergoing primary surgery (PS). A secondary aim was to evaluate if distress could be significantly correlated with patients’ depression and anxiety, and if generalized self-efficacy (GSE) may moderate these relationships. Methods: one hundred and twenty-four BC patients (61 waiting for PS and 63 undergoing NAC), with a mean age of 51.64 (SD = 9.67), were instructed to complete a series of questionnaires evaluating socio-demographic data, anxiety, depression, distress and GSE. Results: An analysis of covariance was conducted, including treatment condition (NAC vs PS) as an independent variable, patients’ distress as a dependent variable, and age as a covariate. A significant mean difference emerged between groups [F(1, 121) = 5.66, p < .05)]. In particular, NAC patients showed a higher distress (Mean = 6.79) than PS ones (Mean = 5.72). Moreover, patients’ distress appeared moderately correlated with both anxiety (r = .34, p < .05) and depression (r = .36 < .05). Finally, results revealed a significant interaction effect of distress and GSE on depression (β = -.19, p < .05), confirming the moderating role of GSE. In particular, for low levels of GSE (-1 SD), the correlation between distress and depression was large and significant (r = .53, p < .001), while for high level of GSE (+1 SD) this relationship was definitively lower (r = .14, p = .03). No significant moderating effects of GSE were found for stress-anxiety relationship. Conclusions: Results of this study seems to confirm that NAC may induce distress in BC patients. Moreover, distress, significantly related to anxiety and depression, may play a detrimental role for patients’ psychological well-being. Finally, GSE emerged as a moderator of distress-depression relationship, suggesting that negative consequences of stress could be reduced during NAC using GSE-based psychological intervention.
Acceptability and effects of values-based outpatient advanced care planning (ACP) in gastrointestinal (GI) cancers.
Authors: Epstein Andrew S. , O'Reilly Eileen Mary , Volandes Angelo E. , Li Yuelin , Shuk Elyse , Breitbart William
Published: September 2018

e21571

Background: We developed and validated the values questions for the Person-Centered Oncologic Care and Choices (P-COCC) ACP intervention, which combines an informational care goals video with a brief patient values interview. Herein, we studied (primarily) the acceptability of P-COCC, and (secondarily) its effects on wellbeing and decisional conflict. Methods: Patients (pts): English-speaking with GI cancer, ≤ monthly followup in MSK medical oncology clinics and believed by their oncologist able to complete study measures and to survive 1-12 months. Consented pts randomized 2:2:1 to P-COCC vs. video alone (V) vs. usual care (UC). Questionnaires: administered baseline and at next follow-up visit on validated measures of wellbeing, and on follow-up only, decisional conflict. P-COCC arm pts also completed 3 Likert scales (was the intervention helpful, comfortable and recommended to others?); a positive score on ≥1 of 3 indicated acceptability for that pt. Results: During screening from 9/2014-11/2016, 202 potentially eligible pts were approached. 51 (25%) declined participation (most common reason, N = 31 = not wanting to discuss the topic). 151 consented and were randomized; 99 (66% of the 151) completed study measures (most common attrition reason, N = 34 = disease progression or death). Of the 99, 63% male; mean age 61 years; mean ECOG PS 1; most common cancer types colorectal, gastroesophageal, and pancreatic; most white race, Christian religion and married. The primary aim was met: Among 33 pts, 32 (97%, 95%CI: 0.84-0.99, p < 0.001) rated P-COCC acceptable. Mean distress scores (0-10) increased (0.43) in the P-COCC arm but decreased in the V (-0.04) and UC (-0.21) arms (p = 0.03 and 0.04, P-COCC vs V and UC, respectively). There were no significant pre-post change scores on other measures of wellbeing (anxiety, depression, stress, acceptance, QOL), or intergroup differences in decisional conflict. Conclusions: Our values-based ACP paradigm is acceptable but may increase distress in GI cancer outpatients. Further studies will investigate underpinnings and follow-up duration of these observations, and ways to best support cancer patients (with any cancers, and regardless of prognosis) in ACP. Clinical trial information: NCT01912131.
Comparison of myocardial strain in cancer patients undergoing chemotherapy with and without anthracycline.
Authors: Zheng Haoyi , Reichek Nathaniel , Way Ann , Toole Rena , Verma Sajal , Mehrotra Bhoomi
Published: September 2018

e21600

Background: Cardiotoxicity has been reported in cancer patients treated with anthracycline- and non-anthracycline-based chemotherapy. Myocardial strain assessed by speckle-tracking echocardiography enables early detection of subclinical chemotherapy-induced cardiotoxicity. However, comparisons of strain indices in patients undergoing chemotherapy with and without anthracyclines have not been reported. The prupose of this study was to compare myocardial strain in patients treated with these two chemotherapy regimens. Methods: This study was approved by the institutional review board at Saint Francis Hospital. 43 adult cancer patients (30 with solid tumors, 6 with lymphomas, 6 with leukemias and 1 with multiple myeloma) treated with anthracyline-based or non-anthracycline-based chemotherapy, were studied with conventional 2D and 3D echocardiography, 2D speckle-tracking imaging, and cardiac biomarkers. Results: Of the 43 patients, 22 received anthracycline-based chemotherapy, with an average cumulative anthracycline dose of 235 mg/m2. The other 21 patients received non-anthracycline-based chemotherapy including VEGF inhibitors and HER-2 receptor antagonists. There was no difference in 2D or 3D left ventricular ejection fraction (LVEF) (60.9 ± 4.5% vs 62.0 ± 4.9% by 2D; 60.5 ± 5.4 % vs 62.1± 5.2% by 3D, p = 0.35 for both 2D and 3D), troponin or NT-proBNP between anthracyline-treated patients and non-anthracycline treated patients. However, global longitudinal strain (GLS) and global circumferential strain (GCS) were decreased in patients treated with anthracycline-based chemotherapy compared with patients treated with non-anthracycline-based chemotherapy (-17.8 ± 2.8 vs 19.9 ± 2.9, p = 0.018 for GLS; -21.6 ± 4.8 vs 24.8 ± 4.8, p = 0.041 for GCS). Conclusions: In contrast with patients treated with non-anthracyline-based chemotherapy, patients treated with anthracyclines had reduced myocardial systolic strain even at low cumulative doses. This occurred in the absence of detectable reductions in LVEF. Thus early assessement of myocardial strain abnormality and early intervention with cardioprotective agents may be considered for these patients.
Room to move: Physical activity and exercise barriers in the cancer clinic.
Authors: Quain Katharine , O'Donnell Elizabeth , Perez Giselle Katiria , Rabin Julia , Park Elyse R. , Peppercorn Jeffrey M.
Published: September 2018

e21601

Background: Exercise can improve outcomes and quality of life following cancer diagnosis. The American College of Sports Medicine (ACSM) recommends 150 minutes of moderate aerobic activity for patients with cancer. We sought to evaluate exercise patterns and barriers to exercise among patients presenting for follow-up care. Methods: Patients were recruited from the outpatient cancer clinic and completed a self-administered survey focused on symptoms, lifestyle and needs. Participants reported height, weight, weekly time performing moderate-to-vigorous aerobic activity, time spent strength training and perceived barriers to exercise. Descriptive statistics characterized the sample and patterns of exercise. An independent-samples t-test examined differences in strength training between patients currently on and off treatment; Chi-square examined differences among those meeting or not meeting ACSM activity guidelines. Results: Of 637 patients surveyed, 590 (93%) completed exercise questions (55% female; median age 60-69). The most common cancer diagnoses were breast (26%), hematologic (18%) and gastrointestinal (12%). Over half (57%; n = 352) were overweight (BMI ≥ 25) and 26% (n = 161) were obese (BMI ≥ 30). Patients engaged in moderate-to-vigorous aerobic exercise an average of 110 min/week and in strength training for 30 min/week. 71% did not meet ACSM aerobic exercise guidelines; 62% reported no strength training and 29% reported no exercise. 76% of respondents reported at least one barrier to exercise. Common barriers included other illness (35%), lack of free time (21%), fatigue (8%) and boredom with exercise (8%). Most participants (60%; n = 351) decreased exercise after cancer diagnosis. Participants currently on therapy were significantly less likely to meet ACSM aerobic activity guidelines (p = 0.04) and reported doing less strength training (p < 0.001) than those not on therapy. Over half of participants (53%) expressed interest in receiving more information about exercise and physical activity services. Conclusions: There is potential to improve activity, fitness and cancer outcomes through increasing exercise among patients with cancer. Accessible, engaging exercise interventions are needed.
The relationship between statins and breast cancer prognosis varies by statin type and exposure time: A meta-analysis.
Authors: Liu Binliang , Yi Zongbi , Guan Xiuwen , Ma Fei , Zeng Yi-Xin
Published: September 2018

e21606

Background:Breast cancer is the most common cancer in females. The effects of statins on breast cancer prognosis have long been controversial, so it is important to investigate the relationship between statin type, exposure time, and breast cancer prognosis. This study sought to explore the effect of statins on breast cancer prognosis. Methods:We searched the MEDLINE, EMBASE, Cochrane Library between October 15, 2016 and January 20, 2017. Searches combined the terms “breast neoplasms[MeSH]”, “statins”, “prognosis” or “survival” or “mortality” with no limit on publication date. Data were analyzed using Stata/SE 11.0. Results: 7 studies finally met the selection criteria and 197,048 included women. Overall statin use was associated with lower cancer-specific mortality and all-cause mortality (HR 0.73, 95% CI 0.59-0.92, P = 0.000 and HR 0.72, 95% CI 0.58-0.89, P = 0.000). Lipophilic statins were associated with decreased breast cancer-specific and all-cause mortality (HR 0.57, 95% CI 0.46-0.70, P = 0.000 and HR 0.57, 95% CI 0.48-0.69, P = 0.000); however, hydrophilic statins were weakly protective against only all-cause mortality (HR 0.79, 95% CI 0.65-0.97, P = 0.132) and not breast cancer-specific mortality (HR 0.94, 95% CI 0.76-1.17, P = 0.174). Of note, more than four years of follow-up did not show a significant correlation between statin use and cancer-specific mortality or all-cause mortality (HR 0.84, 95% CI 0.71-1.00, P = 0.616 and HR 0.95, 95% CI 0.75-1.19, P = 0.181), while groups with less than four years of follow-up still showed the protective effect of statins against cancer-specific mortality and all-cause mortality (HR 0.62, 95% CI 0.44-0.87, P = 0.000 and HR 0.61, 95% CI 0.45-0.80, P = 0.000). Conclusions:Although statins can reduce breast cancer patient mortality, the benefit appears to be constrained by statin type and follow-up time. Lipophilic statins showed a strong protective function in breast cancer patients, while hydrophilic statins only slightly improved all-cause mortality. Finally, the protective effect of statins could only be observed in groups with less than four years of follow-up.
L-carnitine for pegylated-l-asparaginase induced hepatotoxicity.
Authors: Wieduwilt Matthew Joseph , Goodman Aaron , Jonas Brian Andrew , Cassaday Ryan Daniel , Castro Januario E. , Mulroney Carolyn M. , Tzachanis Dimitrios , Ball Edward David
Published: September 2018

e21626

Background: Pegylated-L-asparaginase (PEG-Asp) treatment causes severe hepatoxicity in about 25% of adults. Two case reports suggest that L-carnitine may rapidly reverse PEG-Asp-induced hepatotoxicity. Methods: We retrospectively analyzed data from 11 consecutive patients from 3 centers receiving L-carnitine for PEG-Asp-related hepatotoxicity from 4/2014 to 4/2016. Eligible adults received L-carnitine for hepatotoxicity probably or definitely related to PEG-Asp. Total bilirubin (Tbili), ALT, or AST stabilization was defined as a variation within 10% from baseline maintained for 3 days. Improvement was defined as a decrease of ≥10% the prior day maintained for 3 days. Liver imaging included CT scans or ultrasounds. Results: The majority of patients were male, 91% (Table 1). Imaging on 7 patients showed hepatic steatosis in 2 (29%) prior to PEG-Asp and 5 (71%) after PEG-Asp. Median peak Tbili, ALT, and AST were 15.4 mg/dL (2.3-27.58), 194 IU/L (120-1491), and 119 IU/L (52-1064), respectively. Median days from hyperbilirubinemia to L-carnitine initiation was 4 (1-13). Median L-carnitine dose was 2,000 mg/day (1,880-4,450). Median days until Tbili, AST, and ALT improvement were 6.5 (4-14), 4 (2-19), and 3.5 (1-8), respectively. Median days until Tbili normalization was 34 (4-52). Improvement in Tbili, ALT, and AST within 8 days of L-carnitine was seen in 5, 19, and 11 patients, respectively. No adverse events were attributable to L-carnitine. Conclusions: L-carnitine for PEG-Asp-induced hepatotoxicity was safe and associated with stabilization and improvement in transaminitis and, to a lesser extent, hyperbilirubinemia. See table. [Table: see text]
Preliminary results from CAMEO-PRO study: Complementary and alternative medicine in oncology—Physicians inform oncological patients.
Authors: Bozza Claudia , Gerratana Lorenzo , Basile Debora , Vitale Maria Grazia , Bartoletti Michele , Agostinetto Elisa , Russo Stefania , Bonotto Marta , Cinausero Marika , Fanotto Valentina , Pelizzari Giacomo , Lisanti Camilla , Minisini Alessandro Marco , Andreetta Claudia , Mansutti Mauro , Poletto Elena , Iacono Donatella , Sottile Roberta , Fasola Gianpiero , Puglisi Fabio
Published: September 2018

e21632

Background: It is estimated that about half of cancer patients (pts) use at least one form of (CAM) Complementary and Alternative Medicine in their life but there is a strong reticence of pts in talking about CAM with their oncologist. Aim of this study is to inform pts about CAM. Methods:From April to December 2016, the observational pilot trial “CAMEO-PRO” prospectively enrolled 200 cancer pts that were invited to attend a tutorial about CAM at the Department of Oncology, University Hospital of Udine (Italy). Before and after the seminar, pts were asked to fill a questionnaire reporting their knowledge and opinion about CAM . Results:Median age was 61 years, 141 (72%) women and 53 (28%) men. At study entry, 139 (72%) pts declared they have never been interested in this topic before; 22 pts (12%) revealed the use of a type of alternative therapy and 53 (31%) revealed the use of complementary therapy. Overall, 111 (55.5%) pts participated to the tutorial. Table 1 shows the percentage of response and the opinion’s change about CAM before and after the tutorial. Conclusions:Informative seminars seem to have an impact on patients’ perceptions and opinions about CAM. [Table: see text]
Early palliative care interventions in patients with hematologic malignancies prior to hematopoietic cell transplantation.
Authors: Alamgir M.Ahsan , Wen Sijin , Craig Michael D. , Pedraza Sandra L.
Published: September 2018

e21634

Background: Early palliative care (EPC) interventions have been endorsed by multiple medical societies, mostly for solid tumors but not for hematological malignancies. Patients undergoing hematopoietic stem cell transplantation (HSCT) suffer significant physical and emotional distress affecting negatively their quality of life (QOL). They also receive more aggressive end-of-life interventions than other cancer patients. Few studies have shown the impact of EPC in the pre-transplant phase on post transplant morbidity and mortality. Methods: 53 patients undergoing HSCT were evaluated on the supportive care clinic for symptom and needs assessment using the Edmonton symptom assessment scale (ESAS) to evaluate symptom burden prior to transplant. Consecutive palliative care visits were offered to patients. We also evaluated whether the supportive care clinic (SCC) visits made a difference on hospitalization rate and mortality comparing this group with 108 patient who did not undergo evaluation. Kaplan-Meier method and log-rank test were used in the survival analysis and Fisher’s exact test was used in the data analysis for categorical variables. Results: The most common symptoms reported by patients included: fatigue (4.4), sleep problems (3.7), pain (2.8), anxiety (2.8), well-being (2.7), and drowsiness (2.3). 26% (14) of the patients were followed in the SCC at 3 months. The most common symptoms at that time included fatigue (5.1), pain (4), drowsiness (3.6), sleep problems (3.1), well-being (2.9), and appetite (2.4). Overall mortality for the whole group was 24%. 28% for the palliative care group and 21% for the control group. Odds Ratio for mortality at 3 and 6 months were not significantly different between groups. Differences in hospital admissions were also not statistically significant. Conclusions: EPC in HSCT patients is feasible and may help with symptom detection and control. No effect on mortality or hospital admission rates was found on this study on patients referred for EPC interventions. Prospective studies are needed to clearly define the role of EPC in HSCT patients.
Implementation of a distress/supportive care screening tool in lung and head and neck cancer clinic.
Authors: Pasquinelli Mary , Obilade Sandra , Rosenberg David , Deliu Zane , Shah Aakash , Knightly Eileen , Feldman Lawrence Eric
Published: September 2018

e21646

Background: Identifying and addressing depression, anxiety, and supportive care needs in cancer patients is an emerging standard of care. The Coleman Foundation “Patient Screening Questions for Supportive Care” tool was used with demographic and diagnostic data to investigate the relationships between screening scores. Methods: Lung/head/neck cancer patients at the University of Illinois Cancer Center were screened using the Coleman Foundation tool. This screening tool identified needs in several categories including Patient Health Questionnaire 4 (PHQ-4) scores; practical, family/caregiver, nutritional, treatment, physical, and spiritual/faith/religious concerns; levels of pain, fatigue, physical activity to quantitatively assess patient distress/supportive care needs. Scores were compared with age, sex, race/ethnicity, insurance, cancer type, and cancer stage. Linear regression was used for statistical analysis. Results: We performed initial screening on 164 lung/head/neck patients ages 36-88 (mean 61), with stages IA to IVC (May 2016 to Jan. 2017). Our findings are summarized in below. We found a 1oeffect that racial/ethnic minority status was significantly correlated with higher scores. We found that lung cancer was correlated with higher screening scores than head & neck on initial screen. Medicare insurance was correlated with significantly lower screening scores. Conclusions: Patients with lung/head/neck cancer have significant needs and concerns that go beyond merely treating their cancer. Our findings show that certain demographic groups have especially high burdens in some specific dimensions and that these specific concerns may be predicted based on diagnostic and demographic information. Thus, these findings serve to inform providers as to where and how to focus supportive care for these patient populations. [Table: see text]