bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibitory effect of PAI-I in perifocal and resection line tissues on tumor growth in women with melanoma.
Authors: Rozenko Ludmila Ya. , Frantsiyants Elena M. , Bandovkina Valeria A. , Cheryarina Natalia D. , Pozdnyakova Viktoria V. , Ilchenko Maria G. , Agarkova Elena I. , Maksimova Natalia A. , Kit Oleg I. , Przhedetskiy Yuriy V.
Published: May 2020

e22083

Background: The ability of malignant tumors to invasion and metastasis is associated with increased activity of the plasmin/plasminogen family proteases. The purpose of the study was to analyze changes in the plasmin/plasminogen system in tumors and adjacent tissues in patients with cutaneous melanoma in dependence on their gender. Methods: The study included 13 men and 22 women with cutaneous melanoma pT1-2N0M0. Levels of plasmin (PAP), content and activity of uPA, content and activity of tPA, content and activity of PAI were determined by ELISA in homogenates of melanoma (M), perifocal (P) and resection line (RL) tissues after surgical treatment. All patients gave a voluntary informed consent for the study. Skin tissues obtained from 20 non-cancer patients after plastic surgery served as the control. Results: The maximal PAP content in women was found in M – 16.5 times higher than in control, in RL – twice higher; PAP in all tissues of men was on average 7 times higher than in control. The content and activity of uPA and tPA in M were elevated in patients of both genders: in women by more than 3 times, in men by 4.9 and 3.7 times for uPA, respectively, and on average by 1.4 times for tPA. Increased content and activity of PAI-I were observed only in M of women by 74.6 and 2.3 times respectively, while PAI-I levels in men were similar to control values, and its activity was 2.9 times higher. Content and activity of PAI in P and RL tissues of men did not exceed the norm despite an increased activity of uPA and tPA, while in women they were elevated on average by 4 and 1.8 times, respectively. Conclusions: A local increase in the content and activity of the PAI-I plasminogen activator inhibitor in P and RL tissues only in women is a distinctive gender characteristics that can inhibit the spread of melanoma.
Effect of chronic neurogenic pain on blood levels of hormones in patients with melanoma depending on their gender.
Authors: Pozdnyakova Viktoria V. , Frantsiyants Elena M. , Bandovkina Valeria A. , Rozenko Ludmila Ya. , Ilchenko Maria G. , Agarkova Elena I. , Zakharova Natalia A. , Khokhlova Olga V. , Przhedetskiy Yuriy V. , Przhedetskaya Viktoria Yu. , Kit Oleg I.
Published: May 2020

e22097

Background: Chronic neurogenic pain (CNP) as a comorbid disease is quite frequent, but its effect on malignant diseases is poorly studied. The risk of cutaneous melanoma in women is higher, but the disease course in men is more severe. The purpose of the study was to reveal the effect of CNP on the levels of sex hormones in the blood of patients with melanoma depending on their gender. Methods: Blood levels of estradiol (E2), estrone (E1), progesterone (P4), testosterone (T) and prolactin (PRL) were measured by ELISA in patients with Т3-4NxM0 melanoma (M): 21 women with CNP (pelvic pain - 7, osteochondrosis – 14), mean age 67.2±2.7 years; 17 men with CNP (osteochondrosis), mean age 65.6±3.1 years. The control group included patients with melanoma similar in age, gender and disease stages without CNP. Results: In women with M+CNP, E2 and P4 were decreased by 1.8 times, while E1 was 1.4 times, T – 2 times, PRL – 1.5 times higher, compared to controls. In men with M+CNP, blood levels of estrogens were unchanged, PRL was 2.5 times lower and P4 and T – 1.3 times higher, compared to the corresponding control levels. Conclusions: CNP upregulated blood levels of androgens in both male and female melanoma patients, and caused the inversion of estrogens only in women with the prevalence of E1 over E2. Gender differences in the CNP influence included the elevation of progesterone and a decrease of prolactin in the blood of men, and P4 deficiency with increased prolactin in women with M+CNP. The specific effect of CNP on the hormonal profile in patients with cutaneous melanoma should be considered in choosing antitumor treatment.
MAP2K1/2 and MAP3K14 as a prognostic biomarker on immunotherapy and correlated with immune infiltrates in melanoma.
Authors: Chen Jing , Ye Ting , Xie Wenzhuan , Huang Mengli , Yang Mengmei
Published: May 2020

e22104

Background: Mitogen-activated protein kinase kinase (also known as MAP2K, MEK, MAPKK) and MAP3K are two subgroup of Mitogen-activated protein kinase cascade. MAP2K1/2 and MAP3K14 are members of two subgroup, respectively. Previous study revealed that MAP2K1/2 and MAP3K14 may be a promising therapeutic target for melanoma. However, the association between MAP2K1/2 and MAP3K14 mutant and melanoma remains elusive. In this study, we aimed to elucidate the efficacy of immunotherapy of MAP2K1/2 and MAP3K14 mutant for melanoma by integrated bioinformatics analysis. Methods: Whole-exome sequencing data for a cohort of 110 patients with metastatic melanoma from whom pre-treatment tumor biopsies were download from cBioPortal. Associations between MAP2K1/2 and MAP3K14 mutations and prognosis and TMB are analyzed, and tumor-infiltrating level (TIL) of 18 T-cell subtypes and 6 other immune cells were used to investigate the underlying mechanism. Results: Results showed that MAP2K1/2 and MAP3K14 mutations were associated with an increased progression-free survival (PFS; HR, 0.42; 95% CI, 0.18-0.96; P = 0.0342) and a superior overall survival (OS; HR, 0.28; 95% CI, 0.09-0.90; P = 0.0227) in melanoma with significance at borderline level. TMB levels in melanoma patients with MAP2K1/2 and MAP3K14 mutations were higher than in wild-type patients (P = 0.007). Moreover, TIL revealed distinct immune cells features in the different groups, where immune cells related to infiltrating levels of Neutrophil cells and natural arising regulatory T (nTreg) cells were more prominently enriched in the mutation group while the wide-type group had higher enrichment of Mucosal associated invariant T (MAIT) cells and T helper 2 (Th2) cells. Conclusions: MAP2K1/2 and MAP3K14 mutations may be a potential predictor for better prognosis in melanoma on immunotherapy. Identification of MAP2K1/2 and MAP3K14 mutations by genomic profiling provides a potentially novel and convenient approach for these patients to predict the prognosis, and refines patient’s management in clinical practice.
Perceived value of cancer survivorship care among Asians and Native Hawaiian/Pacific Islanders.
Authors: Acoba Jared David , Tamashiro Sharon , Chock Marci
Published: May 2020

e22522

Background: Numerous studies have evaluated the impact of cancer survivorship care. However, no study to date has focused on Asian or Native Hawaiian/Pacific Islander (NH/PI) cancer survivors. It has been well documented that Asian and NH/PI patients often suffer from inferior cancer outcomes compared to White patients, and differences in their experience with cancer survivorship care could contribute to this disparity. Methods: Surveys were sent to 1410 cancer survivors who were treated at a community cancer center with curative intent and who had received survivorship care plans between Jan 2014 and June 2018. The 26-item questionnaire evaluated patients’ perception of various aspects of their survivorship care plan and follow-up physician visits. All responses were anonymous. Results: Of the 360 patients who responded, 24% were White, 54% Asian, and 13% NH/PI. Compared to Whites, Asian and NH/PI patients were younger (p = 0.004), less educated (p = 0.004), and reported a lower income (p < 0.0005). Among all patients, 62% reported that the survivorship care plan was “very helpful” and 86% rated their satisfaction with physician follow-up visits as “very good” to “excellent.” There were no racial differences in satisfaction with either survivorship care plan or physician follow-up. In a multivariate binary logistic regression, Asians and NH/PI patients were significantly more likely to rate ongoing survivorship care as helpful compared to Whites, OR 4.08 (95%CI, 2.13-7.82). Conclusions: There were no racial differences in patient satisfaction with their survivorship care plans and follow-up care. However, Asian and NH/PI patients valued ongoing cancer survivorship care follow-up significantly more than White patients. Whether more extensive survivorship care would lead to improved outcomes among Asian and NH/PI cancer patients should be investigated further.
Effect of FAmily CEntered (FACE) advance care planning (ACP) on families’ appraisals of caregiving for their teens with cancer.
Authors: Baker Justin N. , Thompkins Jessica , Friebert Sarah , Needle Jennifer , Wang Jichuan , Cheng Yao , Lyon Maureen
Published: May 2020

e22533

Background: Little is known about how well family caregivers respond to participating in pACP. The research objective was to understand the effect of FAmily CEntered pediatric Advance Care Planning (FACE pACP) for teens with cancer (FACE-TC) on families’ appraisals of caregiving for their child over time. Methods: 126 adolescent/family dyads were randomized to either FACE-TC intervention or treatment as usual control. FACE-TC is three weekly, 60-minute pACP sessions with a trained/certified facilitator. Family Appraisal of Caregiving Questionnaire subscales assessed outcomes. Generalized Estimating equations (GEE) model was used to examine outcome change over time. The effect of intervention on the change was examined by the interaction between time and intervention. Results: 126 adolescent/family dyads completed baseline assessments. 102 dyads completed the 3-month assessment. Adolescents were mean age of 17 years (range 14-20); 57% female; 79% Caucasian. Family participants were mean age 46 (range 19-67); 83% female; 82% Caucasian. Positive caregiving appraisals subscale items are “Caring for __ is satisfying; It is a privilege to care for __; Caring for __ has made me feel closer to him/her; I am able to comfort __ when he/she needs it; I feel confident I can handle most problems in caring for __; I feel useful in my relationship with __; I am committed to caring for __”. FACE pACP significantly increased positive caregiving appraisals at 3 months post-intervention, compared to controls, (β = 0.20, Confidence Interval = 0.03-0.37, p = 0.0189). No significant differences were found between groups for the subscales: burden, distress or family well-being. Conclusions: FACE pACP significantly increased positive caregiver appraisals compared to controls. The family caregiver’s role is critical for the well-being of teens with cancer. Findings identified positive aspects of caregiving in the context of pACP without increasing caregiver burden or distress. Clinical trial information: NCT02693665.
Preliminary safety, pharmacokinetics, and efficacy results from an open-label, multicenter, Phase I/II study of avapritinib in Chinese patients with unresectable or metastatic gastrointestinal stromal tumors (GIST).
Authors: Li Jian , Gong Jifang , Wang Xicheng , Li Jie , Li Yan , QI Changsong , Shen Lin , Ren Wenxiao , Zhao Wanqi , Wang Yedong , Hu Jin , Ren Chunli , Song Wenjie , Yang Jianxin
Published: May 2020

e23526

Background: More than 85% of GIST patients (pts) have tumors associated with KIT or PDGFRA mutations. Avapritinib is a potent, selective, small-molecule inhibitor that targets KIT/PDGFRA activation loop mutants. Recently FDA approved avapritinib for pts with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation, including D842V mutations based on a robust ORR (84%) in the NAVIGATOR study. This abstract reports preliminary results from the dose escalation part of the bridging study in Chinese pts with advanced GIST. Methods: Adult pts with unresectable or metastatic GIST that progressed after imatinib and ≥ 1 other tyrosine kinase inhibitor, or could not tolerate the standard treatment or had PDFGRA D842V mutation were enrolled and treated with avapritinib once daily (QD) in continuous 28-day cycles following a modified 3+3 dose escalation design. Primary objectives included determination of Recommended Phase II dose (RP2D) and assessment of safety. PK parameters and response per mRECIST v1.1 for GIST were also assessed. Results: As of 25 Dec 2019, 12 pts were treated with avapritinib QD at a starting dose of 200 mg or 300 mg (6 per group). No dose-limiting toxicities were observed. Most treatment-emergent adverse events (TEAEs) were Grade (G) 1-2, most commonly blood creatine phosphokinase increased (n = 9) and blood bilirubin increased (n = 8). There were no G4-5 TEAEs. The most frequent G3 treatment-related TEAE was anaemia (n = 2). Serious adverse events were observed in 1 pt (renal hydrocele) in 200 mg group and 2 pts (abdominal distension and anaemia) in 300 mg group, all were G3 and considered unrelated to avapritinib. No AEs leading to drug discontinuation occurred. Avapritinib was rapidly absorbed (median Tmax 2.0-4.0 h) and the exposure increased proportionally with doses at the steady state. The mean half-life of avapritinib ranged 42.2-44.4 h, supporting QD dosing. Of the 3 pts with PDGFRA D842V mutation (all in the 300 mg group), 2 pts achieved PR, and 1 had SD, as assessed by investigators at the first tumor assessment. Conclusions: Avapritinib appears generally tolerable at 200 mg and 300 mg QD and shows clinical activity in Chinese pts with PDGFRA D842V mutation. Based on the safety profile in Chinese pts and dose selection results in NAVIGATOR study, 300 mg QD was determined to be the RP2D for Chinese pts. The preliminary safety, PK, and efficacy data support further investigation of avapritinib in Chinese pts with GIST. Clinical trial information: NCT04254939 .
The potential role of extracellular matrix in the activity of trabectedin.
Authors: De Vita Alessandro , Recine Federica , Miserocchi Giacomo , Pieri Federica , Farnedi Anna , Fabbri Francesco , Fausti Valentina , Liverani Chiara , Spadazzi Chiara , Cocchi Claudia , Casadei Roberto , Ercolani Giorgio , Riva Nada , Gurrieri Lorena , Ibrahim Toni , Mercatali Laura
Published: May 2020

e23542

Background: Soft tissue sarcomas (sts) represent a rare group of solid neoplasm of mesenchymal origin with a 1% incidence of all adult cancers. Liposarcoma and leiomyosarcoma (L-sarcoma) are the most common histotypes. The current first-line treatment for advanced/metastatic L-sarcomas is represented by anthracycline based-regimens. Second-line therapy options include trabectedin, eribulin, ifosfamide, gemcitabine and dacarbazine. In particular, the activity of trabectedin, a tetrahydroisoquinoline molecule, as well as its mechanism of action is not completely elucidated. Methods: The study involved six patient affected L-sarcoma. Patient-derived primary cultures were established after patient surgical treatment. Primary cells were cultured in standard monolayer culture and 3D collagen-based scaffolds. In order to gain inside into the mechanism of action of the drugs, genomic-, chemobiogram, proteomic-, cytometer and in silico analysis were performed. Results: The results confirmed the preservation of tumor gene expression in 3D culture model compared to standard monolayer culture. In particular 3D culture system was able to resemble the patient gene expression of TGFb, SLUG, SNAIL, MMP9 compared to 2D. In silico analysis showed an upregulation of COL1A1 gene, the extracellular matrix component of the present 3D model, in sts compared to other tumors. Pharmacological analysis displayed an increased sensitivity to trabectedin in all the 3D L-sarcoma primary culture compared to 2D culture system, while this was not observed with the other drugs. As previous preclinical evidences suggested that trabectedin mechanism of action include the impairing of ECM proteolytic degradation mediated by tumor cells, we think that its high observed sensitivity depend on the presence of collagen in our 3D- model. Conclusions: These results were suggestive of the losing credibility of monolayer standard culture for pharmacology studies and highlight the promising role of 3D patient-derived culture model for the study of sts biology. Moreover these results shed the light on the potential role of ECM in the mechanism of action of trabectedin in L-sarcomas. The work points out the role of this tumor microenvironment component in predicting response to trabectedin and provide the rationale for better stratifying patients which will be candidate for this drug. Further researches are needed to confirm these evidences.
Evaluation of thyroid-stimulating hormone-increased, hypertriglyceridemia and proteinuria as markers of anlotinib efficacy in advanced soft tissue sarcoma.
Authors: Chi Yihebali , Yao Yang , Fang Zhiwei , Wang Shusen , Huang Gang , Cai Qiqing , Shang Guanning , Wang Guowen , Qu Guofan , Wu Qiong , Jiang Yu , Song Jianmin , Chen Jing , Zhu Xia , Cai Zhengdong , Bai Chunmei , Lu Yongkui , Yu Zhihua , Shen Jingnan , Cai Jianqiang
Published: May 2020

e23548

Background: ALTER0203 was a randomized phase IIB trial (NCT02449343) that demonstrated single-agent activity of anlotinib in advanced STS (aSTS). The primary endpoint progression-free survival (PFS) was met and presented as an oral presentation in 2018 ASCO. The most common adverse events with anlotinib were hypertension (62.66%), thyroid stimulating hormone (TSH) increased (56.33%), hypertriglyceridemia (50%), hand-foot syndrome (48.10%) and proteinuria (36.08%) similar to other vascular endothelial growth factor receptor pathway-targeted therapies. We had evaluated the anlotinib-induced hand-foot syndrome and hypertension with clinical outcome in aSTS patients previously. Here we investigated thyroid stimulating hormone increased, hypertriglyceridemia and proteinuria on clinical outcome in aSTS patients treated with anlotinib. Methods: We conducted a review of patients enrolled in ALTER0203. Median PFS was analyzed in patients with thyroid stimulating hormone increased, hypertriglyceridemia and proteinuria vs patients with no thyroid stimulating hormone increased, hypertriglyceridemia and proteinuria. All analyses were exploratory and required cautious interpretation. Results: A total of 158 patients received anlotinib in the ALTER0203 study. During the study, TSH increased was observed in 89 patients (56.33%). Hypertriglyceridemia was observed in 79 patients (50%). Proteinuria was observed in 57 patients (36.08%). Median PFS was longer in patients with TSH increased vs patients with no TSH increased (8.40 vs 4.23 months, p = 0.015). Patients with any grade TSH increased while on anlotinib had an adjusted hazard ratio for progression of 0.64 compared to those without TSH increased. Also, median PFS was longer in patients with hypertriglyceridemia and proteinuria vs patients with no hypertriglyceridemia and proteinuria (8.43 vs 4.13 months, p = 0.002; 8.40 vs 4.37, P = 0.048). Patients with any grade hypertriglyceridemia and proteinuria while on anlotinib had an adjusted hazard ratio for progression of 0.59 and 0.75 compared to those without hypertriglyceridemia and proteinuria respectively. Conclusions: In this retrospective analyses, TSH increased, hypertriglyceridemia and proteinuria can serve as biomarkers in aSTS patients treated with anlotinib. Clinical trial information: NCT02449343 .
Phase II clinical trial of pazopanib for patients with unresectable or metastatic malignant peripheral nerve sheath tumors.
Authors: Nishida Yoshihiro , Urakawa Hiroshi , Nakayama Robert , Ozaki Toshifumi , Ae Keisuke , Matsumoto Yoshihiro , Ando Yuichi , Kuwatsuka Yachiyo , Ueda Takafumi , Kawai Akira
Published: May 2020

e23569

Background: Malignant peripheral nerve sheath tumor (MPNST) is a malignant soft tissue tumor that does not respond well to chemotherapy and often develops on the basis of neurofibromatosis type 1 (NF1). The purpose of this study was to examine the effects of pazopanib on MPNST. Methods: This study was designed as a physician-initiated phase II clinical trial of pazopanib in patients with MPNST with unresectable or distant metastases. Eleven large hospitals were selected from the Japanese Musculoskeletal Oncology Group (JMOG), and patients were registered between July 2016 and August 2018. The primary endpoint was set to clarify the clinical benefit rate (CBR, including complete or partial response and stable disease) at 12 weeks for pazopanib according to Response Evaluation Criteria in Solid Tumors (RECIST1.1). Progression-free survival and overall survival were set as secondary endpoints along with the safety of this treatment. The clinical benefit rate based on Choi evaluation at week 12 was also set as the secondary endpoint. Results: The study enrolled twelve patients with MPNST. Grade 2 was 7 and grade 3 was 5 by according to the FNCLCC evaluation. Median follow-up period was 10.60 (1.74-22.85) months. Six were male, and six were female. Median age was 49 (20-76). After 12 weeks of pazopanib treatment, CBR was 50.0% (6 of 12 patients) and 50.0% (6 of 12 patients) at RECIST and Choi criteria, respectively. The median progression-free survival was 5.4 months for both RECIST and Choi. Interestingly, the median progression-free survival was 2.9 months for patients with FNCLCC Grade 2 and 10.2 months for Grade 3 for both RECIST and Choi. The median overall survival was 10.6 months. The adverse events of Grade 4 was neutropenia in one person and lipase elevation in one person. Grade 3 adverse events observed in ≥10% of patients were increase of AST and ALT, and decrease of white blood cells. Conclusions: The results of this pazopanib clinical trial were comparable to those of previous doxorubicin-based chemotherapy, and better than those of other molecular targeted therapy. Although accumulation of cases is necessary, pazopanib treatment for MPNST might be a safe and promising treatment, particularly for grade 3 MPNST. Clinical trial information: UMIN000019303 .
Current treatment efficacy for metastatic soft tissue sarcoma: A targeted literature review.
Authors: Stirnadel-Farrant Heide , Mahajan Anadi , Dhillon Navdeep , Patel Nashita , Pokras Shibani
Published: May 2020

e23577

Background: Soft tissue sarcoma (STS) is a rare malignancy with an annual incidence rate of < 5 cases per 100,000 persons; outcomes for metastatic STS (mSTS) are poor. A targeted literature review was conducted to quantify the efficacy/effectiveness of current mSTS therapies. Methods: A structured search based on the population, intervention, comparator, outcome, study type (PICOS) framework was performed on articles (2009–2019) in MEDLINE, Embase, and Cochrane Central. Limited congress searches (ESMO, AACR, ASCO 2016–2018/2019) were also conducted. Clinical trials (CT) and observational studies (Obs) involving patients (pts, any age) with advanced mSTS receiving any pharmacological intervention were included. After screening, selected efficacy (CT) or effectiveness (Obs) endpoints (including progression-free survival [PFS], overall survival [OS], overall response rate, and duration of response) stratified by line of treatment (LOT, if available) were extracted. Results: Overall, 85 studies (56 CT, 29 Obs) met inclusion criteria; study size was 20–4,274 pts. PFS and OS (from 70 studies) were reported for pts with mSTS treated with a wide range of interventions including doxorubicin, trabectedin, pazopanib, and gemcitabine. Across any LOT, median PFS ranged 1.5–9.3 months in CT and 2.1–11.0 months in Obs; ranges were 5.7─28.8 months and 7.0─38.6 months, respectively, for OS. Median PFS and OS were generally lower with later (vs initial) LOT; few studies assessed ≥4 LOT (Table). Outcome data (any LOT) for trabectedin and pazopanib (the only approved targeted mSTS treatments) are shown in Table. Conclusions: This review of the efficacy/effectiveness of current treatments highlights the unmet clinical need for therapies that improve survival outcomes in pts with mSTS. Results may be influenced by small sample size, pt population, and care improvements over the period studied. [Table: see text]
Relationship described by bereaved caregivers (BCGs) between blood transfusions and hospice utilization for loved-ones (LOs) who died from acute myeloid leukemia (AML).
Authors: Cripe Larry Dean , Baker Layla , Sargent Katie , Martin Caroline , Cottingham Ann H.
Published: May 2020

e24002

Background: Patients with AML may under-utilize hospice due to a reluctance to discontinue potentially life-sustaining transfusions. Transfusions while on hospice are a proposed solution. Methods: Nineteen BCGs completed brief surveys and participated in semi-structured interviews. Interviews were audio-recorded, transcribed and qualitatively analyzed for content related to transfusions and hospice enrollment. Results: Surveys: Four out of 16 BCGs reported their LOs received transfusions until death. The time between last transfusion and death was within 2 weeks (12/19) and more than 1 month (3/19). BCGs reported the purpose of transfusions in the last month of life was to live longer (6) and/or to feel better (10). Interviews: The research team identified 5 points relevant to any connections between transfusions and hospice enrollment: 1. Only 2 of 19 BCGs described a decision to delay hospice enrollment due to inability to continue transfusions while on hospice. Both reported gaining enhanced knowledge about their LOs prognosis and coming to agreement that transfusions were burdensome and not justified. 2. The majority of BCGs described becoming aware that the doctor discontinued transfusions rather than reporting that the discontinuation of transfusions was a decision made by their LO. 3. BCGs described a “logical” and accepted transition from chemotherapy and transfusions to transfusions alone to no transfusions. 4. BCGs’ perspectives on transfusions evolved from transfusions as necessary to may be helpful to no longer indicated. They recall experiencing and accepting this progression rather than discussing the transition with providers. 5. Several impediments to hospice unrelated to transfusions were identified: rapid decline of LO, no perceived need for hospice, equating hospice with a home-based service, and bias against hospice due to past experiences. Conclusions: The desire for ongoing transfusion support is not a major impediment to hospice enrollment in the experience of BCGs. Providing transfusions on hospice may not address the low rates of hospice utilization.
Efficacy of tumor treating fields (TTFields) in elderly patients with newly diagnosed glioblastoma (GBM): Sub-group analysis of the phase III EF-14 trial.
Authors: Ram Zvi , Kim Chae-Yong , Zhu Jay-Jiguang
Published: May 2020

e24019

Background: Tumor Treating Fields (TTFields) are an anti-mitotic, regional treatment modality, utilizing low intensity alternating electric fields delivered non-invasively to the tumor using a portable medical device. TTFields are FDA-approved for glioblastoma and malignant pleural mesothelioma. In the EF-14 [NCT00916409] phase 3 GBM study, TTFields significantly extended survival in newly diagnosed GBM when added to maintenance temozolomide (TMZ). Elderly GBM patients usually have worse prognosis and often receive only partial treatment for the disease. The aim of the following post-hoc analysis was to examine the effects of TTFields in the elderly population (≥65 years of age) enrolled in the EF-14 study. Methods: All 134 elderly patients (≥65 years of age) from the EF-14’s intent-to-treat population were included in the analysis, Overall survival (OS) and progression-free survival (PFS), as well as adverse events were compared between the TMZ + TTFields arm and the TMZ alone arm. Results: The median age was 69 (range: 65-83), 69% were male. Median PFS from randomization was 6.5 months versus 3.9 months in the TTFields + TMZ versus TMZ alone arms, respectively (hazard ratio [HR], 0.47 [95%CI 0.30, 0.74] P < 0.0236). Median OS was 17.4 months versus 13.7 months in the TTFields + TMZ versus TMZ alone arm, respectively (HR 0.51 [CI 0.33, 0.77] P < 0.020). Serious adverse events (SAEs) were reported in 39% of patients treated with TTFields + TMZ and in 33% of patients treated with TMZ alone. None of the SAEs were considered related to TTFields. SAEs were considered related to TMZ or to the underlying disease. Grades 1-2 skin AEs were observed in 51% of patients. Conclusions: Consistent with the overall outcome of the EF-14 study, elderly patients treated with TMZ + TTFields showed significantly better OS compared to patients on TMZ alone, and without increase in grade 3-4 toxicity. Clinical trial information: NCT00916409 .
Preoperative frailty assessment with Robinson Frailty Score (RFS) and Edmonton Frail Scale (EFS) in older surgical patients with cancer.
Authors: Nishijima Tomohiro F. , Esaki Taito , Morita Masaru , Toh Yasushi
Published: May 2020

e24033

Background: In general geriatric surgical patients, frailty has been shown to predict higher rates of postoperative adverse outcomes. A little is known about how to optimally assess older adults with cancer for preoperative frailty. We evaluated the potential utility of the RFS [Robinson Am J Surg. 2013], EFS [Rolfson Age Ageing. 2006] and Geriatric 8 (G8) for prediction of postoperative adverse events. Methods: This cohort study included older adults who were prospectively evaluated by geriatric oncology service at Kyushu Cancer Center in Japan before undergoing oncological surgery between September 2018 and December 2019. The RFS measures cognition, function (activities of daily living (ADLs) and Timed Up & GO (TUG)), history of falls, comorbidity, albumin and hematocrit (score 0 to 1: fit (n = 71), 2 to 3: prefrail (n = 30) and 4 to 7: frail (n = 13)). The EFS evaluates cognition, function (IADLs and TUG), incontinence, self-perceived health, mood, nutrition, polypharmacy and social support (score 0 to 3: fit, 4 to 7: prefrail and 8 to 17: frail). G8 was dichotomized at previously studied cut-off value of 14. The primary outcome was composite adverse events (AEs), including 30-day postoperative complications (Clavien-Dindo grade ≥ 2) and discharge to an institutional care facility. Severity of surgery was assessed using the Operative Stress Score (OSS) [Shinall JAMA Surg. 2019]. Results: Of 114 patients (median age 80 years, range 72-96), surgery type was GI in 62%, HEENT in 20%, GYN in 8%, and other in 10%. 100 patients had ECOG PS 0 to 1. Using the OSS, surgical procedures were classified as very low to low stress (9%), moderate stress (31%), high stress (46%) and very high stress (15%). 45 patients had AEs. After adjusting for the OSS, preoperative frailty based on the RFS was associated with the occurrence of AEs (fit: 25%, prefrail: 49%, frail: 77%; p < 0.01). However, neither the EFS (fit: 30%, prefrail: 37%, frail: 60%; p = 0.14) nor G8 was significantly associated with a risk of AEs (score > 14: 17%, score ≤ 14: 41%; p = 0.07). Conclusions: Preoperative frailty status defined by the RFS is predictive of postoperative adverse outcomes in older adults undergoing elective surgery for cancer.
Effects of community-based supervised exercise in the quality of life, physical fitness, and functioning of breast cancer survivors.
Authors: Alves Alberto , Viamonte Sofia , Amarelo Anabela , Garcia Catarina , Antunes Pedro , Duarte Barbara , Vieira Micael , Teixeira Madalena , Tavares Ana , Lopes Ricardo , Mendanha Patricia , Martins Maria , Leão Inês Isabel , Marinho Joana Catarina Lima , Helguero Luisa , Capela Andreia , Joaquim Ana
Published: May 2020

e24035

Background: Physical exercise is recommended to cancer patients. We aim to evaluate the efficacy of a low-cost community-based supervised exercise program in early breast cancer survivors after primary treatment. Methods: A single-arm clinical trial, controled by a run-in period, of a 16-weeks intervention consisting of 3 weekly sessions of combined aerobic and strength exercise at moderate to vigorous intensity in group classes of no more than 20 participants. Participants were evaluated at weeks 1, 8 and 16 (M1, M2 and M3) of the run-in period and 8 and 16 of the experimental phase (M4 and M5) for quality of life (QoL) (EORTC QLQ-C30), handgrip strength, sit-to-stand (STS) test and maximal aerobic capacity. Results: Of the 82 participants, 25 completed the program and evaluations. Median age was 58 years (39-73), 64% underwent mastectomy, 48% had axillary lymph node dissection, 80% was treated with radiotherapy, 80% with chemotherapy and 84% with hormonotherapy. Median time from surgery was 13 months (4-107). Physical functioning domain of QoL improved significantly following 8 (p = 0.04) and 16 weeks (p = 0.03) of exercise training. Handgrip strength in surgical and non-surgical limbs increased after 8 weeks and maintained after 16 weeks of control phase, further increasing after 8 weeks (p = 0.01) and 16 weeks of exercise (p = 0.00). Lower-limb strength also increased after 16 weeks of exercise (p = 0.01), and maintained during control (p = 0.09). Additionally, maximal aerobic capacity tended to further increase after exercise training (p = 0.06), after increasing during control phase (p = 0.02). Conclusions: A low-cost community-based supervised exercise program improves physical fitness and functioning in breast cancer survivors after primary treatment. Clinical trial information: NCT04024280 . [Table: see text]
Unmet supportive care needs and health behaviors in Hispanic/Latino cancer survivors with cardiometabolic comorbidities.
Authors: Moreno Patricia , Ramirez Amelie G. , Penedo Frank J.
Published: May 2020

e24038

Background: Cardiometabolic illness is a leading cause of death among cancer survivors previously treated for early-stage breast, prostate, and colorectal cancer. Despite the fact that Hispanics/Latinos in the U.S. are at a significantly elevated risk for poor cardiometabolic health, there is a paucity of research examining cardiometabolic comorbidities in Hispanic/Latino cancer survivors. The aim of this study was to examine unmet supportive care needs and health behaviors in Hispanic/Latino cancer survivors with and without comorbid peripheral vascular disease and diabetes. Methods: Hispanics/Latinos diagnosed with breast, prostate, or colorectal cancer (N = 288) were assessed using the Charlson Comorbidity Index, Supportive Care Needs Survey, and ACS Lifestyle Behavior Scale within 15 months of treatment completion in an NCI-funded project. Logistic regression analyses were conducted adjusting for sociodemographic and medical covariates. Results: Most survivors had a high school education or less (65.6%) and a household income less than $50,000 (68.4%) and were foreign-born (59.4%) and either monolingual Spanish-speaking (54.2%) or English-Spanish bilingual (26.0%). One-quarter (24.7%) were diagnosed with comorbid diabetes and one-fifth (20.8%) were diagnosed with comorbid peripheral vascular disease. Survivors with peripheral vascular disease were more likely to have unmet health system and information needs (OR 2.29, p = .011) and unmet sexuality needs (OR 2.07, p = .020) and marginally more likely to have unmet psychological care needs (OR 1.71, p = .099) than those without peripheral vascular disease. Survivors with diabetes were more likely to have unmet sexuality needs (OR 2.06, p = .015) than those without diabetes. Survivors reported increasing some positive health behaviors following their diagnosis of cancer, including regular health check-ups (61.5%) and consumption of healthy foods like fruits and vegetables (61.8%). However, attempts to lose weight (45.1%), exercise (40.6%), and avoid alcohol (26.0%) and cigarettes (17.0%) were less common. Health behaviors did not vary between survivors with and without peripheral vascular disease and diabetes (p > .05). Conclusions: Comorbid peripheral vascular disease and diabetes are highly prevalent among Hispanic/Latino cancer survivors and are associated with greater unmet supportive care needs. Targeted efforts are needed to increase exercise and weight loss as well as reduce smoking and alcohol consumption in Hispanic/Latino cancer survivors.
Dashboard directed decision support to increase cancer survivorship care plan adherence.
Authors: Rizeq Yazan , Brackett Casey , Yousef Rawan , Hebal Ferdynand , Budds Susan , Rao Ruta D. , Levy Mia Alyce
Published: May 2020

e24043

Background: Oncology practices face multiple challenges when trying to implement the Commission on Cancer (CoC) Survivorship Care Plan (SCP) documentation standard. First, it is difficult to systematically identify patients who qualify for a SCP from the electronic medical record (EMR). Second, SCP documentation must be completed within a specific timeframe that does not always align with clinical encounters for routine care. Finally, as practices participate in more regulatory programs, such as the Oncology Care Model (OCM), the burden of meeting the unique but often overlapping documentation standards becomes burdensome. Our goal was to improve adherence to SCP documentation through enhanced clinical documentation workflows and clinical decision support. Methods: To meet CoC SCP standards, SCP templates were built into the EPIC EMR at a single multi-centered institution. These templates allowed the user to indicate on the problem list if the SCP was needed. Likewise, Institute of Medicine (IOM) care plan documentation templates and reminders were built to meet OCM standards. Population dashboards were developed in Tableau to track SCP documentation adherence and provide support regarding eligible patients who required SCP documentation. Patients were eligible who had a cancer diagnosis codes on the problem list, and MC in the EMR. Patients greater than 12 months from being marked curative were considered eligible to complete SCP. Results: Between 2015-2019, 2763 cancer patients were MC by 31 providers, where 806 (30%) were OCM patients. Overall, 1372 (70%) non-OCM patients required an SCP, where 563 (41%) were completed. When examining the OCM patients, 689 (85%) required a SCP, where 552 (80%) were completed. For patients MC in 2018, 163/439 (37%) and 137/190 (72%) of patients received a SCP for the non-OCM and OCM group respectively. For patient MC in 2019 after implementation of the decision support dashboard, 115/145 (79%) and 144/148 (97%) of eligible patients had completed SCP for the non-OCM and OCM group respectively (Table). Conclusions: During the study period, adherence to SCP documentation doubled concordant with CoC standards at that time. Integration of IOM and SCP documentation improved adherence among OMC compared to non-OCM patients. The decision support dashboard helped prioritize cases for SCP documentation for care teams. This is an example of a decision support framework that could be used for other standards driven documentation requirements in cancer.
Health behaviors (HBs) among head and neck cancer (HNC) survivors.
Authors: Jacobs Linda A. , Blauch Abigail N. , Pucci Donna A. , Palmer Steven C
Published: May 2020

e24044

Background: HNC affects more than 59,000 Americans annually and is mediated by HBs both in terms of etiology and long term outcomes. Health behaviors in this population, however, have not been well described. This project describes HBs as a first step in developing appropriate interventions to improve health and, ultimately, outcomes among HNC survivors. Methods: Potential participants were identified through the tumor registry at the Abramson Cancer Center as well as affiliated sites. Eligibility included: a) Diagnosis and treatment of HNC; b) Aged 18 to 70 years; c) more than 1 year post-diagnosis; d) Confirmation of human papillomavirus (HPV) status; e) Ability to understand written English. Potential participants were sent an explanation of the study, informed consent, a self-reported questionnaire, and a self-addressed stamped envelope for return of materials. HBs included items recommended by Glasgow et al. assessing diet, aerobic activity, strength-flexibility, leisure time activity, smoking, alcohol consumption, and access to a physician. Results: 451 individuals were found to be eligible and approached. 102 (23%) agreed to participate and usable data were collected from 93 participants. The sample was predominantly white (96%), male (80%), middle aged (M = 59 yrs), married (82%), college educated (63%), and 63% reported an annual income of greater than $100,000. 74% were HPV positive. Although current smoking was rare (7%), historical use of tobacco was common (48%). Current alcohol use was also common (65%) with an average of 12 days per month in which alcohol was consumed. Participants reported an average of 2.1 drinks per day. Binge drinking was reported by 22% of those who drank, with an average of 3.5 binge drinking sessions per month. Scores on our measure of nutritional behavior range from 0-16 with lower scores indicating better nutrition. The sample mean was 7.1. According to body mass index (BMI) 59% were overweight or obese. With respect to the overall sample, 59% reported adequate aerobic exercise and 64% adequate strength and flexibility. In terms of leisure time activity, 18% would be classified as sedentary, 19% as moderately active, and 64% as active. All participants reported having a current primary care physician and 92% reported having had a physical examination in the previous 12 months. Conclusions: Binge drinking and BMI appear to be the most common negative HBs in this population, although there remain opportunities to improve dietary and exercise behaviors, as well.
Improve, a community-based exercise intervention versus support group to improve functional and health outcomes among older African American and non-hispanic white breast cancer survivors from diverse socioeconomic backgrounds: Recruitment strategies and baseline characteristics.
Authors: Owusu Cynthia , Nock Nora , Hergenroeder Paul F. , Austin Kris , Bennett Beth , Cerne Stephen , Moore Halle C. F. , Petkac Jean , Schluchter Mark D. , SCHMITZ KATHRYN H. , Webb-Hooper Monica , Wimbley Leonard , Coccia Sarah , Nagy Caitlin , Berger Nathan A.
Published: May 2020

e24052

Background: We conducted an exercise study to IMPROVE health outcomes in older breast cancer survivors (BCS) from diverse racial and socioeconomic backgrounds. Here, we report cohort recruitment strategies and baseline characteristics. Methods: ‘IMPROVE’ is a randomized trial, designed to evaluate a group-based exercise intervention compared to support group. Participants were ≥ 65 years, had stage I-III breast cancer and within five years of treatment completion. Enrollment target was 220 participants, 25% in each of four strata defined by race (AA versus Non-Hispanic Whites [NHW]) and SES (low vs. high). Participants were recruited through hospital-based tumor registries, the state tumor registry or direct referrals. Results: Between October 2016 and November 2019, 7487 patients were screened, 4790 were potentially eligible, 230 were consented and 213 randomized into the study. The Eligible-to-Randomization rates were 4.4% overall, and 84%, 8%, and 2% for recruitment utilizing direct referrals, hospital and state registries, respectively. Median age of the randomized cohort was 70 years (range: 65-88 years) and included 25% AA/Low SES, 20% AA/High SES, 19% NHW/Low SES and 36% NHW/High SES Older BCS. Compared with registry-eligible patients, directly referred patients were more likely to be AA vs. NHW (41% vs. 19%, p = 0.003) and to accept study participation (88% vs. 16%, p < 0.0001). Conclusions: Direct referrals resulted in the highest recruitment yield and was the most effective strategy for recruiting AA patients. Behavioral intervention studies seeking to target older BCS from racial minority and SES disadvantaged backgrounds should focus on strategies that foster direct referrals to study participation. Clinical trial information: NCT02763228 .
Impact of breast cancer chemotherapy on ovarian damage and recovery.
Authors: Goldfarb Shari Beth , Bedoschi Giuliano , Turan Volkan , Crown Angelena , Abdo Nadia , Dickler Maura N. , Oktay Kutluk
Published: May 2020

e24059

Background: As societal shifts have led to more women delaying childbearing, a diagnosis of breast cancer is increasingly more likely to occur prior to the completion of family building. Therefore, understanding impact of chemo on future fertility is of the utmost importance. This study evaluates the trends in AMH over time in women receiving different chemo regimens for breast cancer. Methods: This is an IRB approved prospective study of 164 women, < 45 years old with non-metastatic breast cancer who were enrolled at time of diagnosis. Patients received chemo and had prospective serum AMH measured at baseline,12, 18 & 24 mos post-chemo. Of those, 99/164 completed 2-yr follow up. Pts were divided according to their chemotherapy regimen: ddAC-T, CMF and other (e.g. TH). Results: Mean age in ddAC-T (n = 118), CMF (n = 22) and other (n = 23) chemo groups were 37.1±4.6, 41.1±3.2 and 37.6±4.3 yrs, respectively (p = 0.001). AMH sharply declined between baseline & 12 mos post-chemo in all groups (p = 0.005). There was no difference in rate of decline between the groups, after adjusting for age. Age was an important predictor of AMH. Older age at study entry was associated with lower AMH with a decrease of 9% per life year (p = 0.0005). AMH recovered from 12 to 18 mos post-chemo in all groups. 18 mos after chemo, AMH recovery was observed in 61%, 59% & 65% in ddAC-T, CMF & other groups, respectively. In the ddAC-T arm there was a 1.9 fold increase in AMH while there was a 1.4 and 3.3 fold increase in the CMF and other arms, respectively. At 2-yrs post-chemo, AMH recovery rate reached 67%, 69% & 77% in ddAC-T, CMF & other groups, respectively. However, 12% in ddAC-T and 23% in CMF had undetectable AMH. Baseline AMH was 1.59 fold higher in pts whose AMH increased compared to those whose AMH decreased between 12 & 18 mos (p = 0.035). AMH recovery was associated with higher baseline AMH. Age, BMI & chemo type did not correlate with AMH recovery and tamoxifen treatment did not impact AMH recovery. Conclusions: Our data show that anthracycline plus taxane, taxane-based and CMF chemo regimens compromise ovarian reserve in breast cancer patients in similar fashion. As surviving ovarian follicles resume production of AMH, most of ovarian reserve recovery occurs by 18 mos post-chemo with some minor recovery from 18-24 mos. Baseline AMH level is the most important predictor of AMH recovery. Hence in women undergoing gonadotoxic chemo, ovarian reserve should be assessed by AMH before and 12 months after treatment to determine extent of damage. The novel information provided in this study is valuable for counseling cancer pts about fertility preservation. Clinical trial information: NCT00823654 .