bluuebunny/crossref_metadata_2025 huggingface dataset:
First phase implementation of cardio-oncology program in the middle-income country of Costa Rica at Hospital Metropolitano healthcare system.
Authors: Wiernik Andres , Pakonen Jessica , Flores Luis Diego , Preinfalk Giselle , Arab Graciela , Sprok Jose , Fernandez Loretta , Lami Leonardo , Solano Carlos , Acuña Raquel
Published: May 2020

e24091

Background: Developing a cardio-oncology program in a middle-income country like Costa Rica can present unique opportunities and challenges. Hospital Metropolitano is a health care system in Costa Rica with a network of two hospitals, 36 clinics, and over 150,000 patients enrolled in its health plan, Medismart. Here we summarize our program, and the initial results of the implementation phase, hoping that institutions with similar resources in low-and-middle-income countries will use this as guidance to develop their own cardio-oncology program. Methods: A cardio-oncology committee was established in May 2019 and includes medical providers, clinical coordinators, administrative workers, and nursing and laboratory staff. A 4-month pre-launch period was established to create an institutional protocol after we reviewed guidelines and literature from similar programs in the United States and Europe. The protocol targets both active cancer patients undergoing treatment and cancer survivors. The program was launched in September 2019 and is currently in the first phase of implementation. Results: During the first phase of implementation, the program was limited to the outpatient setting and patients were referred exclusively by the medical oncology providers from our health care system. In this period, 28 patients met criteria for referral and all enrolled according to our protocol. The median age of our patients was 49 (range 16-77). 25 patients (89%) were female and 20 (71%) had a diagnosis of breast cancer. At the time of enrollment, 21 (75%) were receiving active cancer treatment and 7 (25%) were identified as cancer survivors. All patients are being followed prospectively. A committee review at the end of the first phase of implementation revealed that the most important challenges that the program needs to address for the second phase of implementation include the following: 1) patient education and outreach, 2) cost of care associated with the interventions recommended by the protocol, and 3) data tracking/registry given the lack of an electronic medical record. Conclusions: Our program represents a real-life experience of the challenges and opportunities that institutions in middle-income countries need to consider when launching such initiatives. To our knowledge, this is the first cardio-oncology program formally established in Central America and we are committed to continue to measure our outcomes prospectively and share these with the global oncology community.
Peripheral neuropathy after breast cancer: An analysis of data from the Women’s Health Initiative Life and Longevity After Cancer cohort.
Authors: Kamgar Mandana , Assad Hadeel , Hastert Theresa A. , McLaughlin Eric , Reding Kerryn , Paskett Electra D. , Bea Jennifer W. , Shadyab Aladdin H. , Neuhouser Marian L. , Nassir Rami , Crane Tracy E , Sreeram Kalyan , Greenwald Mark K. , Simon Michael S.
Published: May 2020

e24093

Background: There are over 3.8 million breast cancer survivors in the United States, and many experience long-term side effects from chemotherapy. Factors associated with peripheral neuropathy (PN), one troubling side effect, following breast cancer among women are unknown. Methods: We included 2,420 women enrolled in the Women’s Health Initiative and diagnosed prospectively with local or regional stage breast cancer and followed in the Life and Longevity After Cancer (LILAC) study. PN was assessed by response to the baseline LILAC questionnaire regarding the presence of “nerve problems, tingling sensations” after treatment. Data were collected on initial course of therapy (surgery, radiation, and chemotherapy) through Medicare linkage or the LILAC staging and treatment form. Chi-square and Wilcoxon rank-sum tests were used for univariate comparison of socio-demographics, clinical and diagnosis characteristics associated with the presence or absence of PN. Results: The sample included 1,913 women (79%) with local and 507 women (21%) with regional stage disease. Initial course of therapy included either surgery alone (21%), surgery and radiation (53%), or surgery and chemotherapy (+/- radiation) (26%). Seventeen percent of women reported experiencing PN days (30%), months (46%) or years (24%) following treatment. Three-quarters (74%) reported ongoing symptoms at the time of the LILAC survey. PN was reported by 33% of chemotherapy recipients, compared to 12% in the surgery alone group, and 11% in the group that received surgery and radiation (p<0.0001). The prevalence of PN was higher among women receiving regimens containing paclitaxel (52%) and docetaxel (39%), compared to those receiving other chemotherapy (17%) (p<0.0001). Conclusions: PN is an important complication of taxane-based chemotherapy. Further analysis will explore the relationship between socio-demographic, clinical and treatment on the development, timing of, and severity of PN after cancer directed therapy.
The chemo-brain effect in colorectal cancer patients.
Authors: Lee Matilda , Chong Wan Qin , Tan Hon Lyn , Chan Gloria , Ho Jingshan , Sundar Raghav , Chee Cheng Ean , Nasrallah Fatima , Koo Edward H , Yong Wei-Peng
Published: May 2020

e24095

Background: The chemo-brain effect associated with systemic chemotherapy results in cognitive disturbances impacting the capacity to engage in tasks and quality of life (QOL). Patients with colorectal cancer (CRC) who receive adjuvant chemotherapy generally have long survival times. The long-term effect of chemotherapy on cognition is uncertain. We aimed to ascertain the frequency of long-term cognitive impairment using neuropsychological assessments and correlating with neuroimaging. Methods: In this prospective pilot study, patients (n=22) with stage II to III CRC between 45 to 75 years old, who were planned to receive adjuvant chemotherapy, were recruited. 3 visits were scheduled for each subject – pre-chemotherapy (V1), at 1 month post chemotherapy (V2), and at 6 months post chemotherapy (V3). Serial tests were performed – the Cambridge Neuropsychological Test Automated Battery (CANTAB), QOL questionnaires (Hospital Anxiety and Depression Scale (HADS), Perceived Deficits Questionnaire (PDQ), EORTC QLQ-C30, FACT-ES), 3 item pocket smell test, functional PET/MRI brain imaging, and blood biomarker studies. Results: 18/22 subjects (13 male, 5 female) had completed tests at all 3 visits; the median age was 62 years (range 51 – 69). 9/18 had an initial decline (median -0.033) of Rapid Visual Information processing (RVP) at V2; 3/9 showed improvement to baseline at V3. 8/18 had a persistent decline in RVP scores at V3 (median -0.054). This was associated with increased HADS depression scores (mean 3.63 at V2 vs 4.63 at V1), worsening attention scores (mean 4.38 at V3 and 3.63 at V1), prospective memory scores (mean 3.75 at V3 vs 3.38 at V1), and total scores (mean 14.63 at V3 vs 13.75 at V1) on the PDQ. 7/18 had an increase in Paired Associates Learning (PAL) errors (median +6) at V2. 3/7 improved to baseline at V3, while 4/7 continued to have a persistent decline. PAL scores were not associated with worsening retrospective or prospective PDQ memory scores, changes in HADS depression or EORTC QLQ-C30 scores. There was no difference in baseline CANTAB scores for patients reporting declining vs stable QLQ-C30 scores. Conclusions: Only half of patients with initial RVP A and PAL decline improved at 6 months post chemotherapy. Further efforts should be placed to identify those at risk of poor recovery, and develop strategies to manage the chemo-brain effect. The correlation of cognitive decline with neuroimaging will be presented in the final analysis.
A retrospective single-center evaluation of the safety and efficacy of direct oral anticoagulants versus low molecular weight heparin in patients with cancer-associated thrombosis.
Authors: McShane Melissa , Senchak Jordan , Stack Anthony , Frimpong Justina , Hellerslia Van T , Zhao Huaqing
Published: May 2020

e24102

Background: Over the past decade, there has been an increase in the use of direct oral anticoagulants (DOACs) in the cancer population despite limited data comparing its use against low molecular weight heparin (LMWH), the standard of care in cancer patients. Increasing data supporting DOACs in cancer-associated thrombosis has emerged over the past few years. Nonetheless, this study will evaluate the relative safety and efficacy of DOACs versus LMWH in cancer-associated thrombosis within an urban setting associated with low socioeconomic status. Methods: This is a retrospective chart review of medical records from patients treated at an urban academic medical center from October 2010 through October 2018. Patients met study inclusion if they had a diagnosis of venous thromboembolism occurring after the date of diagnosis of active cancer and were prescribed a direct oral anticoagulant (rivaroxaban, apixaban, dabigatran, edoxaban) or a low molecular weight heparin (dalteparin, enoxaparin, or fondaparinux) as monotherapy for the treatment of venous thromboembolic disease. Patients were excluded if they had less than 6 months of follow up data for reasons other than death. The primary outcomes were recurrent venous thromboembolism, major bleeding and death. Results: Of the 914 patients who met inclusion criteria, 286 were excluded due to lack of follow up data. The remaining patients included 472 in the LMWH arm and 156 in the DOAC arm. At 6 months, recurrent thromboembolism occurred in 5 of the 472 patients (1.1%) in the LMWH group as compared with 4 of the 156 patients (2.6%) in the DOAC group (p = 0.170). Major bleeding occurred in 36 patients (7.6%) in the LMWH group and 11 patients (7.0%) in the DOAC group (p = 0.813). Death within 6 months of starting anticoagulation occurred in 76 patients (16.1%) in the LMWH group and 16 patients (9.6%) in the DOAC group (p = 0.046). Discontinuation before 6 months of treatment occurred in 241 patients (51.2%) in the LMWH group and 46 patients (29.5%) in the DOAC group. Conclusions: The LMWH and DOAC groups had similar rates of recurrent thromboembolism and major bleeding. The mortality rate within 6 months of starting anticoagulation was significantly higher in the LMWH group and this difference requires further evaluation. These results help support the continued use of DOACs for the treatment of cancer-associated thrombosis and demonstrate that DOACs are as safe and effective as LMWH in this patient population.
PDGFC signaling is a potential therapeutic target for radiation proctopathy.
Authors: Fang Lekun , Xie Yunling , Zou Shaomin , Yang Ziqing
Published: May 2020

e24105

Background: Radiation proctopathy(RP), with acute or chronic rectal dysbiosis, arises as one of the most crucial complications of radiation therapy for pelvic malignancies. Common symptoms of RP patients include rectal breeding, incontinence and so on. However, its efficacy is disappointing due to lack of specific therapeutic drugs. Moreover, limitied scientific studies have been carried out to elucidate the mechanism of RP progression. Herein, we aim to study the underlying mechanism of RP with mouse model and clinical samples, and dig out its potential therapy. Methods: Firstly, chronic radiation proctopathy(CRP) mouse model is established by administering 25 Gy γ-irradiation in the pelvic region shielding the rest of bodies with lead blocks. Eight weeks later, the mice are harvested, and their colorectal tissues are used for RT-qPCR, western blot, immunostaining and transcriptome sequence analysis. Secondly, the outcomes of irradiated Pdgfc+/+ and Pdgfc−/− mice are compared and gene set enrichment analysis(GSEA) is used to further clarify the differences between these two groups. Lastly, crenolanib, a selective inhibitor of PDGFR, is subjected to mice before or after γ-irradiation to study its potential role in RP prevention and treatment. Results: In our RP mouse model, pdgfc and fibrosis markers are shown to highly express in the distal colorectal tissues after irradiation, Similarily, accumulation of PDGFC and fibrosis-related proteins is observed in RP patients’ tissues and serum. Besides, pdgfc appears in the list of cytokine and cytokine receptor interaction gene set which is the most enriched one in the radiation group. Furthermore, pdgfc knockout significantly alleviates radiation induced colorectal injuries in vivo, including mucosal lesions, submucosal thickening, and hyperplasia and edema of muscular layer. Moreover, GSEA reveals that pdgfc knockout may suppress RP progression through repression of pro-inflammatory cytokines and chemokines. Finally, crenolanib overcomes irradiation-induced injuries in the colorectal region of mice. Conclusions: PDGFC is an important regulator of RP progression, which may serve as a potentially therapeutic target for RP treatment.
Knowledge, attitude and practices regarding the use of medical cannabis: A national survey among Israeli oncologists.
Authors: Mirelman Dan , Waissengrin Barliz , Goldway Noam , Sharon Hagai , Brill Silviu , Wolf Ido
Published: May 2020

e24125

Background: Despite lack of clinical trials reporting on beneficial effects of the cannabis plant for cancer-associated symptoms, its use is increasing worldwide. Approximately 10,000 Israeli cancer patients receive permits for the use of medical cannabis, making cannabis one of the most commonly prescribed oncology treatments in Israel and making the Israeli oncologists highly experienced with its use. The experience gained by the Israeli oncologists is therefore highly valuable. Methods: We conducted a web-based survey among all 238 Israeli oncologists, addressing personal experience; knowledge and attitudes toward the use of cannabis in oncology. Results: Response rate was 54% (n = 126), with the vast majority (87%) regularly prescribing cannabis to their patients. Anorexia, pain and nausea were the most common indications for cannabis use. While 90% of responders stated lack of sufficient knowledge regarding cannabis, its use was perceived as effective and safe. Interestingly, while most oncologists stated that opioids should be used as a first line treatment for cancer pain, most would prefer cannabis for pain relief if needed by a close relative. Oncologists who support cannabis legalization were more likely to prescribe it. Conclusions: Our findings indicate extensive use and perception of medical cannabis despite lack of knowledge, and support about efficacy and indicate a unique role for moral attitudes affecting clinical decisions. These data call for the implementation of an educational program and practical guidelines enabling more consistent and rational approach toward cannabis role in oncology.
Patient-reported and clinician-rated performance status and general health among women with gynecologic cancers on palliative chemotherapy.
Authors: Poort Hanneke , Thompson Embree , Lu Gang , Keating Nancy Lynn , Matulonis Ursula A. , Campos Susana M. , Horowitz Neil S. , Dinardo Margaret , Carlson Kenzie , Onnela Jukka-Pekka , Wright Alexi A.
Published: May 2020

e24128

Background: Oncologists’ perceptions of patients’ performance status (PS) and general health are key determinants of eligibility for chemotherapy and clinical trials. We sought to examine correlations between patient-reported and clinician-rated Eastern Clinical Oncology Group PS (ECOG-PS) and general health status (EQ5D) in women with incurable recurrent gynecologic cancers, as well as step counts from accelerometry as a proxy for objective PS. Methods: We used baseline data from a randomized trial evaluating a mobile health intervention that collects patient-reported outcomes and passive smartphone data and provides tailored symptom management advice. Half of participants also received a wearable accelerometer. We calculated Pearson correlations to determine agreement between ECOG-PS and EQ-5D assessments in patient-clinician dyads. We also calculated the median (IQR) step counts among a subset of women with ≥7 days of ≥8 hours wear time. Results: Data from 78 patient-clinician dyads demonstrated a moderate correlation between patient-reported and clinician-rated ECOG-PS (r = .47; P< .000). Among dyads, 38 (49%) had perfect agreement; 36 (46%) had higher patient-reported ECOG-PS, indicating more patient-reported functional limitations, compared with clinician reports; and 4 (5%) had lower patient-reported ECOG-PS. Comparisons between patient-clinician ratings of EQ-5D subscales indicated moderate agreement for mobility (r = 0.44; P< .001), pain/discomfort (r = 0.45; P< .001), and usual activities (r = 0.36; P= .002); and weak or no agreement for anxiety/depression (r = 0.31; P= .007) and self-care (r = 0.02; P> .05). Participants’ daily step counts varied widely (median = 5,511 steps, IQR = 3,784, range 1,736-13,961) and were not associated with patients’ or clinicians’ ECOG-PS estimates (r = -.12; P= 0.44 and r = -0.03; P= 0.84) or patient-reported mobility (r = -0.10; P =0.51). Conclusions: Among women with incurable gynecologic cancers, patients’ and clinicians’ perceptions of patients’ ECOG-PS were moderately correlated, although 46% of clinician ratings were more optimistic than patients’ ratings. There was also moderate agreement between dyads for mobility and pain/discomfort. Patients’ step counts were not correlated with ECOG-PS or patient-reported mobility. Future studies should examine these measures longitudinally to determine which is the most sensitive predictor of clinical outcomes. Clinical trial information: NCT03022032 .
Cannabidiol: Assessing preclinical safety in ovarian and endometrial carcinoma cell lines.
Authors: Rush Shannon , Kapur Arvinder K , Patankar Manish S. , Barroilhet Lisa Marie
Published: May 2020

e24130

Background: Cancer patients use cannabidiol (CBD) for chemotherapy and cancer symptoms, though research of CBD safety and efficacy for these conditions are ongoing and mixed. We sought to determine endometrial (ECC1) and epithelial ovarian cancer (Kuramochi) cell proliferation when exposed to different concentrations of CBD, for the broader goal to establish if CBD can safely be utilized to treat the symptoms of cancer, including those caused by chemotherapy. Methods: ECC1 and Kuramochi cells were kept in media (RPMI with 10% bovine serum and 1% penicillin/streptomycin). We passaged cells when > 90% confluent by adding tryspin-EDTA, incubating at 37C for 3 minutes, then spinning down with media to harvest the cell pellet. Cells were re-suspended in media, counted and apportioned to 96 well plates. Plates were incubated at 37C x 24 hours. CBD (from Cayman Chemical) was suspended in DMSO per manufacturer instruction then used to treat cells x72 hours at different concentrations (2.5-50uM). MTT was added to cells, cells incubated at 37C x 3 hours, media and MTT were removed and DMSO was added. Optical depth (OD) was calculated for plates using SoftMaxPro version 6.2.2. ODs were used to calculate inhibitory concentration for 50% cell death (IC50). Results: Kuramochi and ECC1 demonstrated decreased cell proliferation when exposed to CBD for 72hours. ECC1 IC50 fell between 2.5-5uM. Kuramochi IC50 fell between 15-20uM. Nearly all ECC1 growth was inhibited at concentrations 10uM or greater. Kuramochi proliferation was 15% that of controls at concentrations of 40 and 50uM CBD. Conclusions: ECC1 and Kuramochi cells demonstrated decreased proliferation in the presence of CBD. This bodes well for future studies of concurrent exposure to CBD and cytotoxic chemotherapy. Further preclinical research needed on CBD effects in endometrial and ovarian cancer, as patients turn to CBD for symptomatic relief from cancer and chemotherapy side effects. [Table: see text]
Moderate to vigorous physical activity effect on chemotherapy-induced peripheral neuropathy.
Authors: Kanzawa-Lee Grace , Krauss John C. , Ploutz-Snyder Robert , Larson Janet , Resnicow Ken , Lievense Athena , Kavanagh Lauren , Smith Ellen M. Lavoie
Published: May 2020

e24151

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common intractable side effect of oxaliplatin treatment that presents with numbness, tingling, and nerve pain in both hands and feet; and sometimes, weakness and impaired balance and quality of life. Moderate-vigorous (MV) physical activity (PA) may reduce CIPN by improving blood circulation, chemotherapy distribution, inflammation, oxidative stress, and neuroplasticity. This dose-response analysis aimed to explore the effect of different MVPA and total PA doses on CIPN severity among oxaliplatin-receiving gastrointestinal cancer survivors. Methods: The original pilot RCT tested an 8-week home-based brisk walking intervention versus PA education alone to reduce CIPN. This analysis focuses on the intervention group ( n = 29), which received MVPA motivational supports (e.g., a Fitbit Charge 2, walking plan, motivational interviewing). Participants completed self-report CIPN severity surveys at baseline (2nd oxaliplatin infusion) and 8 weeks. Fitbit-classified minutes of weekly MV and daily total (light-vigorous) PA were averaged over the 8 weeks. MVPA was dichotomized: met 225 weekly MVPA minutes ( n = 17) or not ( n = 19). Linear regression was used to analyze the effect of MVPA/total PA changes and effects on 8-week CIPN severity, controlling for oxaliplatin dose received and baseline CIPN levels. Results: Increases over the 8 weeks were observed in patients’ MVPA (mean difference [ MD] = 17.39 min/week; 95% CI 1.38, 33.40; p = .03) and total PA ( MD = 7.80 min/week; 95% CI 2.31, 13.29; p = .01). Total PA had no effect on the outcomes. However, averaging at least 225 MVPA minutes per week led to less severe sensory CIPN ( MD = -7.28; 95% CI -13.53, -1.03; p = .03), particularly tingling in the hands ( MD = -26.35; 95% CI -44.03, -8.68; p = .01). The models accounted for 37% and 44% of the variance in sensory CIPN ( p = .02) and tingling at 8 weeks ( p = .01), respectively. Conclusions: This pilot study provides preliminary evidence that increasing weekly MVPA, specifically, may lead to reduced CIPN severity among gastrointestinal cancer survivors receiving oxaliplatin. A larger study that utilizes stronger MVPA measurement and biomarker evaluation is needed. Clinical trial information: NCT03515356 .
Effect of growth differentiation factor 15 (GDF-15) inhibition on energy balance in cancer cachexia and in lipopolysaccharide (LPS)-induced sepsis mouse models.
Authors: Breen Danna , Bennett Donald , Jagarlapudi Srinath , Joaquim Stephanie , Zou Chang , Patel Anita , Wu Zhidan , Seeley Randy , Zhang Bei Betty , Bezy Olivier
Published: May 2020

e24153

Background: Growth differentiation factor 15 (GDF-15) is a cytokine that induces anorexia, weight loss and has been reported to be associated with cachexia and poor survival in illnesses characterized by inflammation such as cancer cachexia and heart failure. In preclinical cancer cachexia models, GDF-15 inhibition has been demonstrated to reverse cachexia and improve survival. Circulating GDF-15 is also elevated in patients with sepsis and is associated with increased complications and poor survival. However, the role of infection- and sepsis-induced GDF-15 in mouse models is controversial based on published reports. Methods: In this study, we examined the effect of GDF-15 inhibition on tumor and lipopolysaccharide (LPS)-induced anorexia, weight loss, and survival using a GDF-15 neutralizing antibody (mAB2) and GDF-15 knockout mice. Results: mAB2 efficacy was confirmed by reversing AAV-GDF-15-induced weight loss in wildtype mice. A cachectic (anorexia and weight loss) mouse tumor model was established with subcutaneous implantation of mouse renal cell carcinoma (RENCA) cells. The chemotherapy sorafenib was administered to slow tumor progression. Plasma GDF-15 was increased to ~2 ng/mL, similar to levels in cancer patients. Treatment with mAB2 rapidly reversed both anorexia and weight loss in the tumor-bearing mice. LPS injection (intraperitoneal, 5 mg/kg) increased circulating GDF-15 in wildtype mice reaching concentrations like that reported in septic patients within 90 minutes and remaining elevated after 48 hours (~1 ng/mL). LPS decreased food intake, body weight, and increased mortality (~20%). Different from the tumor model, GDF-15 neutralization with mAB2 did not prevent or exacerbate any of the effects of LPS. There were no observed detrimental effects of mAB2 treatment in either model. Similarly, in GDF-15 knockout mice the LPS effect on energy balance and survival was comparable to that observed in wildtype controls. Plasma GDF-15 was undetectable in the GDF-15 knockout mice. Conclusions: Taken together, these data suggest that GDF-15 is a critical regulator of energy balance and survival in selective pathophysiological states associated with weight loss.
Evaluation of emergency department visits in patients treated with immune checkpoint inhibitors.
Authors: Guven Deniz Can , Sahin Taha Koray , Aksun Seren , Taban Hakan , Aktepe Oktay Halit , metin Aksu Nalan , Akkas Meltem , Erman Mustafa , Kilickap Saadettin , Dizdar Omer , Aksoy Sercan
Published: May 2020

e24160

Background: Immune checkpoint inhibitors (ICIs) are the main drugs for immunotherapy. Their efficacy comes at the expense of adverse events including immune-related adverse events (IRAEs). The emergency department (ED) is an important encounter point in the cancer care. However, the data on the causes of ED visits is scarce. Therefore, we evaluated the ED visits of patients treated with ICIs and tried to determine the predisposing factors. Methods: We performed a retrospective review of adult cancer patients treated with ICIs for any cancer type between 09/2014 and 06/2019 in Hacettepe University Cancer Center. The data about ED visits after the first dose of ICIs to six months after the last dose of ICIs was collected from the hospital registries. Baseline characteristics, stages and types of patients’ tumors, types of ICI, causes for emergency visits and hospital admissions were recorded. Results: A total of 221 patients were included. The median age was 60.7 years (18-86) and 65.6% of patients were males. Median follow-up was 9 months (0.2-55). Nivolumab was the most common immunotherapy (67.9%). Melanoma was the most common diagnosis (27.6%) followed by kidney and lung cancer. 90% of patients had advanced disease and more than half of patients were treated with two or more lines of therapy. The 83 patients (37.6%) had at least one emergency department (ED) visit. Half of these visits resulted in hospital admissions. Thirty-eight patients had more than one ED visits with 14 patients having three or more ED visits. Immune-related adverse events comprised less than 10% of the ED visits with most of the ED visits were related to symptoms attributable to disease burden itself. The median time to ED visit after the first dose of ICI was 126 days. While baseline ECOG status, age, polypharmacy (defined as the regular use of five or more drugs), concomitant chemotherapy, eosinophilia and lactate dehydrogenase levels didn’t significantly increase the risk, patients with regular opioid use and baseline neutrophilia ( > 8000) had a statistically significant risk of ED visits (p values 0.001 and 0.19 respectively). These two factors remained significant in the multivariate analyses. Conclusions: In this study, almost 40% of ICI treated patients had ED visits. Recognition and addressing of this patient group’s problems in the ED is very important as evidenced by ability to discharging half of patients from the ED. Collaboration between the other specialists like emergency medicine specialists is vital for improving the care of patients treated with immunotherapy.
“Where did you read that?” External sources of information and patients perceptions of prognostic goals.
Authors: Patell Rushad , Einstein David Johnson , Miller Eric James , Halleck Jennifer , Dodge Laura , Buss Mary K.
Published: May 2020

e24166

Background: Patients receiving palliative cancer treatment frequently misperceive likelihood of benefits/toxicity. Physicians fear that external sources of information regarding treatment enhance misperceptions and complicate decision-making. We investigated the sources of external information used, how much it affects patients' misperception and influences their treatment choices. Methods: We prospectively surveyed patients with advanced solid cancers and their oncologists regarding benefits/risks of palliative therapies including likelihood of tumor response and toxicity. Patients reported information-seeking behavior pre-treatment. We compared patients’ perceptions of benefits/risks to that of their oncologists. Results: Across four disease groups, 119 eligible patients enrolled. Their median age was 65 years (range 59–73), 55% were male, and 56% had undergone prior treatment. Treatments included chemotherapy (61%), targeted therapy (15%), and immunotherapy (24%). Over two thirds, 69% of participants stated that they wanted as much as possible information from their oncologist, and nearly all (95%) stated that they felt the amount of information provided by their clinician was “just right.” However, 60% wanted at least a moderate amount of information from external sources, and 58% reported obtaining information from sources other than their oncologist. The most common external sources of information used by participants were printed materials (35%), word of mouth (26%), the American Cancer Society (24%), and WebMD (21%). Nearly one in 3 (31%) of participants felt the information from external sources influenced their decisions more than a small amount. There was no correlation between self-education and misperception of tumor response (coefficient -0.04 p = 0.6) or of treatment toxicity (coefficient 0.05, p = 0.6) relative to their treating physicians’ estimates. Conclusions: While many patients sought information from external sources, most felt they were not substantially influenced by this information. Almost all felt their oncologists provided them with adequate information. Information-seeking behavior was not associated with greater misperception regarding the treatment goals/expectations. Thus, despite a common concern about misinformation in external information sources, oncologists should support patients who seek such sources and discuss their findings.
Accuracy of oncology patients’ expectations of cure.
Authors: Shin Paul , Romano Danielle R. , Bernal Camila , Knezevic Andrea , Desai Anjali V. , Nelson Judith Eve , Epstein Andrew S.
Published: May 2020

e24167

Background: Efficacy of chemotherapy in gastrointestinal (GI) cancers is a well-studied endpoint. Patients require a realistic understanding of likely benefits to make informed treatment decisions. Prior studies show that patients with incurable cancer do not understand the palliative role of treatment. Patient understanding of chemotherapy intent (curative v. palliative) across all stages of GI cancers and modifying factors is unknown. Methods: Ambulatory clinic patients with GI cancers newly presenting for treatment answered validated questions on illness and treatment intent1 as part of an initiative integrating palliative care at diagnosis regardless of stage. Patients were asked to estimate probability of cure from chemotherapy with Likert responses (range ‘not at all likely’ to ‘very likely’). Two experienced oncologists (GI medical and surgical) independently assessed accuracy of patient response after reviewing patient data and grade one clinical evidence. (E.g. Patient with locally advanced stage II rectal cancer who felt chemotherapy was "somewhat likely" to be curative deemed to be 'accurate') Responses were coded as accurate or inaccurate and accuracy was compared between clinical factors with Chi-square test. Results: For 113 patients, median age was 59, 62% were male, 55% had stage IV disease. Patients were diagnosed with colon (27%), anorectal (25%), pancreatic (21%), biliary (13%), or other GI cancer (14%). There was 99% clinician agreement rating accuracy. 51 (45%) patients responded accurately. Accuracy was lower in stage IV vs. stage I-III disease (35% v 57%, p=0.02), lower in unresectable vs. resectable disease (32% v 64%, p=0.001) and higher in adjuvant vs. non-adjuvant setting of chemotherapy for stage I-III patients. (80% vs. 42%, p=0.007) Accuracy did not differ significantly by gender, age, cancer, prior surgeon visit or DNR status. Conclusions: Inaccurate perceptions about likelihood of cure with chemotherapy are prevalent across all stages of GI cancers, but particularly amongst patients with advanced GI cancer. Patients receiving adjuvant chemotherapy were more likely than metastatic patients to have accurate understanding. Next steps include mixed methods analysis of qualitative data from this cohort to evaluate factors driving inaccurate understanding of treatment. 1Weeks J et al. “Patients’ expectations about effects of chemotherapy for advanced cancer.” NEJM 367 (2012): 1616-1625.
Neural mechanisms of impaired executive function in untreated colorectal cancer patients.
Authors: Anderson David , Garlinghouse Matthew , Hauger Arica , Moody Alison , Berger Ann M. , Grem Jean L.
Published: May 2020

e24170

Background: Cancer-related cognitive impairment (CRCI) affects 45% of colorectal cancer (CRC) patients prior to treatment. This study aimed to explore the neural mechanisms of CRCI in this severely understudied population by using a combination of neuropsychological and cognitive neurophysiology assessments. Methods: Newly diagnosed Stage I-IV CRC patients were recruited at a Midwestern tertiary medical center. Enrollment criteria included normal or corrected to normal vision and no prior cancer within 3 years. Healthy comparisons were recruited and demographically-matched to Stage III/IV patients scheduled to receive chemotherapy. Participants completed neuropsychological measures of processing speed, psychomotor speed, executive function, and verbal memory at study baseline. We recorded scalp electroencephalography while participants performed a computer-based cognitive task designed to measure control over spatial attention. Two event-related potentials were measured following presentation of a task-irrelevant spatial cue: (1) N2, a neural correlate of stimulus selection emerging approximately 160 milliseconds after stimulus presentation; and (2) N2pc, a neural correlate of spatial attention allocation emerging approximately 200 milliseconds after stimulus presentation. Results: CRC patients were enrolled within 4-8 weeks following surgery for Stage I (11%), II (31%), and III (35%) CRC; Stage IV patients (23%) started chemotherapy without surgery. Patients (n = 26) and controls (n = 14) were matched on age and gender; patients were trending toward lower education than controls (p = .06). Patients performed worse than controls on executive function assessments (Trials B: p = .049; Stroop: p = .025). N2 amplitudes were smaller in patients than controls (p = 0.032. N2pc amplitudes were larger in patients than controls (p = .092). N2 amplitudes were associated with Stroop interference scores (r = 0.50, p = .068). Conclusions: CRC patients demonstrated impaired executive function performance at baseline. Neurophysiological data suggest impairments may emerge from limited neural resources available for stimulus selection and poor control over spatial attention. Correlations between neurophysiological data and executive function performance suggest participants better able to overcome task-irrelevant interference had relatively more neural resources available for stimulus selection. Overall, these results suggest patients may be limited in their ability to focus their attention on caregiver and health care team instructions. Clinical trial information: NCT03683004 .
Lessons on humanity: The voice of cancer patients through a literary contest.
Authors: Niewiadomski Darío , Gil Deza Ernesto , Gercovich Daniela , Gil Deza Lourdes , Acuna Claudia Lorena , Smolje Leonel , Ares Sandra L. , Gercovich Natasha , Marin Ordoñez Alba , Muino Marcelo , Danussi Inés , Tognelli Flavio , Dragosky Marta , Morgenfeld Eduardo L. , Rivarola Edgardo G. J. , Gercovich Felipe G.
Published: May 2020

e24189

Background: Most cancer narratives are provided by skilled American and British writers (Broyard, Hitchens, Jobs, Kalanithi, Pausch, Sacks, Sontag or Wishart). This paper highlights the voice of ordinary Latin American patients who wrote about their experience. Methods: Between February 2, 2019 and March 3, 2019, the first author encouraged cancer patients to narrate their experience with the disease for an online literary contest (“ www.oncologiaesperanzadora.com ”). After studying all submissions, we grouped attitudes, feelings, metaphors and descriptions used in different domains related to the course of the disease. A text-mining study was conducted to identify the context of keywords in each of the domains. Results: In total, 224 literary works were submitted to the contest. Characteristics of the population: sex F/M: 184/40; age at time of contest: 53 yo (18-82); time between diagnosis and submission to contest: 8 y (1-73); country of origin: Argentina (201), other countries (23); diagnosis: breast (130), hematological (15), colorectal (13), melanoma (6), lung (5), head and neck (5), kidney (3), other (47). The table shows keywords found in each of the domains. Conclusions: 1) Cancer patients are willing to share their story if they are given the opportunity. 2) Through the narratives of the disease, it is possible to study its impact on patients’ lives and the different coping strategies. 3) Reading the experience of patients with the disease in their own voice is a valuable instrument for medical education. [Table: see text]
Effect of informational charts on patient understanding of nontherapeutic research procedures in phase I trials.
Authors: Campbell Gavin Paul , Abernethy Eli Rowe , Cook John W. , Lohani Minisha , Lewis Colleen Margaret , Switchenko Jeffrey M. , Dixon Margie D , Harvey Donald , Pentz Rebecca D.
Published: May 2020

e24193

Background: It is difficult for patients to distinguish non-therapeutic from therapeutic procedures in research. In phase I trials, day 1 pretreatment biological samples are used for research and care; posttreatment samples are for research purposes only. Preliminary data suggested patients did not understand this difference. Our study tested to see if a simple information chart would improve understanding of the nontherapeutic research procedure. Methods: A sequential two arm study was conducted. Controls (C) were asked whether samples taken at different times on day 1 of the trial were to be used for their care, for research only, or for both. The experimental (E) group provided patients with a study-specific information chart labeling the purpose of required samples and patients were then asked the same questions. Results: 100 patients (50 each C and E) were interviewed after consenting to a trial. Patients were mostly white (63%), male (53%), with an annual income > $60,000 (51%); 49% had a college degree. In both arms, understanding that pretreatment samples were for patient care and research was moderate (50% C; 62% E). Understanding that posttreatment samples were for research was significantly higher in the experimental arm (16% C; 44% E p = 0.002). Conclusions: Questions regarding the purpose of biological samples taken pre-administration of study drug were less susceptible to therapeutic misconception due to the “both” option being true. Since the provision of an informational chart significantly improved understanding of the purpose of the posttreatment sample, we suggest that providing such a chart may help alleviate this type of therapeutic misconception. [Table: see text]
A phase II study evaluating atezolizumab (A), cobimetinib (C), and vemurafenib (V) in patients (pts) with BRAF-mutant melanoma and central nervous system (CNS) metastases (mets).
Authors: Queirolo Paola , de la Cruz Merino Luis , Abajo Guijarro Ana Maria , Tawbi Hussein Abdul-Hassan , Dummer Reinhard
Published: May 2020

TPS10081

Background: CNS mets, a common complication of melanoma, are associated with poor survival prognosis (median of 4-5 months). The rationale for combining PD-L1 pathway blockade using atezolizumab (A) with the small molecule BRAF pathway–targeted inhibitors cobimetinib (C) and vemurafenib (V) for the treatment of BRAFV600 mutation–positive melanoma is based on preclinical and translational evidence supporting the synergistic antitumoral effects of these approaches. Recently, the phase 3 IMspire150 study (NCT02908672) demonstrated improved progression-free survival outcomes with A + C + V vs C + V. Methods: This phase 2 study (NCT03625141) is currently evaluating A + C + V in pts with BRAFV600 mutation–positive advanced melanoma and CNS mets. The study originally included a parallel cohort evaluating A + C in pts with BRAFV600wild-type advanced melanoma and CNS mets. This cohort was closed at an enrollment of 15 pts after the primary analysis of the phase 3 IMspire170 study (NCT03273153), which showed no added benefit with A + C vs pembrolizumab in pts with BRAFV600 wild-type disease. Eligible pts are aged ≥18 years with histologically confirmed melanoma and magnetic resonance imaging–confirmed brain mets ≥5 mm in at least 1 dimension. In addition, pts should not have received prior systemic treatment for metastatic disease; they were required to have ECOG performance status ≤2 and adequate hematologic and end organ function. Prior stereotactic or surgical therapy of ≤10 brain mets is allowed. The primary endpoint is intracranial objective response rate (ORR) with A + C + V in BRAFV600mutation–positive melanoma as assessed by an independent review committee. Key secondary endpoints include investigator-assessed intracranial ORR, extracranial ORR, overall ORR, safety, and quality of life. Exploratory biomarker analyses are planned. The sample size for the cohort will be approximately 60 pts. No formal statistical hypothesis is being tested in this study. The primary study analysis and the analyses of all efficacy endpoints and safety summaries will be based on data collected ≤6 months after the last pt is enrolled. Clinical trial information: NCT03625141.
A phase Ib study of endogenous SLC45A2-specific cytotoxic T cells for the treatment of patients with metastatic uveal melanoma.
Authors: Phillips Suzanne , Lizee Gregory , Brown Courtney , Lara Jacqueline Marie , Bassett Roland L. , Beal Lisa G , Murthy Ravi , Talukder Amjad , Hawke David H , Lai Ivy , Hwu Patrick , Yee Cassian , Patel Sapna Pradyuman
Published: May 2020

TPS10086

Background: Overall survival (OS) for patients (pts) with advanced uveal melanoma (UM) is poor with a median survival of approximately 12 months. Roughly half of all pts with UM will develop distant metastatic disease despite effective treatment of the primary site. Metastatic UM has a 90% prevalence of liver involvement. Currently, there are no specific FDA-approved treatments for metastatic UM and consensus guidelines recommend participation in a clinical trial. Modern treatments such as checkpoint inhibitors and targeted therapy have less impressive outcomes in UM. Our group has identified peptide epitopes of SLC45A2, a melanosomal transport protein, that is highly expressed in UM and present at very low levels in normal melanocytes. We demonstrated that cytotoxic T cells against SLC45A2 were able to kill HLA-matched UM cell lines. Through the use of enabling technologies, SLC45A2-specific cytotoxic T cells can be isolated and expanded ex-vivo from peripheral blood for use in endogenous T cell (ETC) therapy (a form of adoptive cellular therapy). These activated ETCs can then be infused to traffic to tumor sites. CTLA4 is a T-cell surface protein that binds to B7 with a higher affinity than the costimulatory receptor CD28, providing an inhibitory signal to T-cells. Anti-CTLA4 blockade can divert this inhibition and release the brake on antigen-specific T-cell activation of ETC. We hypothesize that antigen-specific ETCs infused via hepatic artery will be safe and tolerable for UM pts with liver metastasis. Methods: We are conducting a first-in-human clinical trial (NCT03068624 ) of ETC therapy targeting SLC45A2 in combination with anti-CTLA4 in pts with metastatic UM. Pts who express HLA-A*02:01 or A*24:02 undergo apheresis to collect T cells. Their cells then undergo ex vivo cloning and interleukin-21 primed expansion. Hepatic arterial infusion of ETCs will ensure direct localization to the target organ of interest. Conditioning with low-dose cyclophosphamide (300 mg/m2) occurs on Day -2. Hepatic arterial infusion of ETCs on Day 0 is followed by low dose subcutaneous interleukin-2 (IL-2) twice daily for 14 days. The initial dose escalation phase is a 3+3 design with a starting dose level of 3.3 x 109 cells/m2 of ETCs alone. Once the maximum tolerated dose of ETCs is established, the dose expansion phase will include ETCs in combination with anti-CTLA4 (Ipilimumab). The primary objective is to evaluate the safety of this first in human T cell regimen. Secondary objectives are to evaluate the in vivo persistence and anti-tumor efficacy. Clinical trial information: NCT03068624.
A phase II study of neoadjuvant pembrolizumab and lenvatinib for resectable stage III melanoma: The neopele study.
Authors: Gonzalez Maria , Menzies Alexander M. , Pennington Thomas , Saw Robyn PM , Spillane Andrew J. , Stretch Jonathan , Shannon Kerwin Frank , Ch'ng Sydney , Nieweg Omgo E. , Cruzado Rojas Maria , Osorio Monica , Rawson Robert V , Ferguson Peter M. , Rizos Helen , Lo Serigne , Scolyer Richard A. , Long Georgina V.
Published: May 2020

TPS10088

Background: Recent clinical trials of neoadjuvant (neo-adj) ipilimumab combined with nivolumab (OpACIN & OpACIN-neo) in resectable stage III melanoma show that a pathological response ( < 50% viable tumour at the tumour bed as determined by histopathological analysis) is associated with a prolonged relapse-free survival compared to no pathological response. Furthermore, recurrences seldom occur in those who have a pathological response following neo-adj immunotherapy with only 1/71 pts (1.4%) having recurred. In contrast, 15/23 (65.2%) pts with no pathological response have relapsed to date. The NeoPeLe trial will test the hypothesis that the synergistic combination of PD-1 blockade (pembrolizumab) with anti-angiogenic/multiple RTK inhibitor (lenvatinib) will result in a high rate of pathological response in the resected surgical specimen with a low rate of toxicity. Tissue and blood biomarkers are drawn at several timepoints and correlated to clinical and pathological endpoints to explore mechanisms of response and resistance. We will compare pathological response rate, and other clinical outcomes in this study, with previously published neo-adj clinical trials to select the best schedules for larger-scale clinical testing. Across neo-adj studies, we will also analyse the tissue collected to explore determinants of the optimal therapy for individual pts, whilst minimising toxicity. Methods: Eligible pts with stage IIIB/C/D, resectable and measurable (RECIST 1.1) nodal metastatic melanoma will be enrolled to this phase II single-centre trial (n = 20). All pts undergo complete nodal resection (RES) at wk 6 following neo-adj therapy with pembrolizumab (200mg, IV, 3 wkly) and lenvatinib (20mg, oral, daily). Adjuvant therapy with pembrolizumab is given for 46 wks after RES. After 52 wks of the study treatment, pts will be followed for relapse and survival for 5 years. CT and FDG PET/CT are used to measure response and exclude progression in the neo-adj phase, and to monitor for recurrence during adj and post treatment phases. Blood and tumour samples are collected at baseline, day 8, RES and at relapse if feasible. Faecal samples are collected at baseline and before RES. The primary endpoint is the complete pathological response rate at RES following 6 wks of neo-adj therapy. Secondary endpoints include RECIST response, metabolic response, OS, RFS, safety/tolerability, surgical outcomes, quality of life, and biomarker analyses. Clinical trial information: NCTNCT04207086.