bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase IB study of lenvatinib (E7080) in combination with temozolomide for treatment of advanced melanoma.
Authors: Hong David S. , Andresen Corina , Mink Jennifer , Ren Min , O'Brien James P. , Nguyen Ly Minh , Falchook Gerald Steven , Kurzrock Razelle , Nemunaitis John J.
Published: March 2020

8594

Background: Lenvatinib is an oral tyrosine kinase inhibitor targeting VEGFR1-3, FGFR1-4, RET, KIT and PDGFRβ. In phase I studies of lenvatinib partial responses were observed in melanoma as well as thyroid, endometrial, and renal cancers. Methods: Patients (pts) with stage 4 or unresectable stage 3 melanoma were treated in sequential cohorts of escalating doses of lenvatinib by continuous once daily dosing and temozolomide (TMZ) days 1-5 every 28 days. Cohort 1: lenvatinib 20mg, TMZ 100 mg; cohort 2: lenvatinib 24 mg, TMZ 100 mg; cohort 3: lenvatinib 24 mg, TMZ 150 mg. Adverse events were recorded according to CTCAE v3.0 and tumor response assessed according to RECIST 1.0. Results: 32 pts were treated: cohort 1: 6 pts, cohort 2: 4 pts, cohort 3: 22 pts. Demographics: median age: 58; males: 63%. Dose limiting toxicities occurred in 0/6 pts in cohort 3 leading to cohort expansion to a total of 22 pts to enable more extensive assessment of toxicity and a preliminary estimate of efficacy. The most common treatment related adverse events in the cohort 3 were fatigue: 50% (gr3: 9%), hypertension: 50% (gr3: 9%), proteinuria: 50% (no gr3), vomiting: 46% (no gr3), hypothyroidism: 46% (no gr3), anorexia: 41% (no gr3), nausea: 41% (no gr3), diarrhea: 36% (gr3: 5%), thrombocytopenia: 32% (no gr3). No treatment-related gr4 events were reported in these categories. The best overall responses per RECIST were partial responses: 5/22 (23%) for cohort 3 pts and 6/32 (19%) for all pts treated at all dose levels. Six-month progression free survival (PFS) rate was 37% and median PFS was 5.4 months. PK/PD analysis and correlation of response with genetic mutational status (BRAF mutations in 31% pts; NRAS mutations in 19% pts) will be presented. Conclusions: Lenvatinib 24 mg once daily in combination with TMZ 150 mg days1-5 every 28 days was given without apparent worsening of either lenvatinib or TMZ related toxicities. Modest clinical efficacy for this combination was observed.
MicroRNAs induced in melanoma treated with combination targeted therapy of temsirolimus and bevacizumab.
Authors: Wagenseller Aubrey G , Shada Amber L , D'Auria Kevin , Murphy Cheryl F. , Sun Dandan , Molhoek Kerrington R. , Papin Jason A , Dutta Anindya , Slingluff Craig L.
Published: March 2020

8597

Background: Targeted therapies directed at commonly overexpressed pathways in melanoma have clinical activity in numerous trials. Little is known about how these therapies influence microRNA expression, particularly with combination regimens. A better understanding of how microRNAs are altered with treatment may contribute to understanding mechanisms of therapeutic effects as well as mechanisms of tumor escape from therapy. Methods: Using microRNA arrays, we analyzed microRNA expression levels in melanoma samples from a Cancer Therapy Evaluation Program-sponsored phase II trial of combination temsirolimus and bevacizumab in stage III or IV melanoma, which elicited clinical benefit in a subset of patients. Seventeen patients were treated with temsirolimus for one week, then combination of both temsirolimus and bevacizumab. Metastatic melanoma biopsies were evaluated days 1, 2, and 23. Tumor samples were evaluated from 12 patients. Results: microRNA expression remained unchanged with temsirolimus alone; however, expression of 15 microRNAs was significantly upregulated (1.4 to 2.5-fold) with combination treatment, compared to pre-treatment levels. Interestingly, twelve of these fifteen microRNAs have been reported to possess tumor suppressor capabilities in various cancer types, including melanoma. We identified 15 putative oncogenes and B7-H3, IGF-1, and IGF-1R as potential targets of the 12 tumor suppressor microRNAs, based on published experimental evidence. For 18 of 25 pairings of microRNA and target-mRNA, changes in gene expression from pretreatment to post-combination treatment samples were inversely correlated with changes in microRNA expression, suggesting a functional effect of the microRNA changes induced by combination therapy. Clustering analysis based on selected microRNAs revealed signatures characteristic of clinical response to combination treatment and of tumor BRAF mutational status. Conclusions: We have identified microRNAs that may be involved in the mechanism of action of combination temsirolimus and bevacizumab in metastatic melanoma, possibly through inhibition of oncogenic pathways.
Preoperative peripheral blood lymphocyte/monocyte ratio and survival in patients with resected stage IV melanoma.
Authors: Rochet Nicole M. , Porrata Luis F. , Kottschade Lisa A. , Grotz Travis Edward , Markovic Svetomir
Published: March 2020

8600

Background: The prognosis of stage IV melanoma patients remains poor. Published results have suggested that components of the complete blood count have significant prognostic value in several malignancies. Among the most studied were the absolute lymphocyte count (ALC), and absolute monocyte count (AMC) on clinical outcomes of patients with lymphoid malignancies. Thus, we sought to investigate if the pre-operative ALC (ALC-PO), AMC (AMC-PO) and ALC/AMC ratio (ALC/AMC-PO) affects the risk of disease recurrence and survival after complete surgical resection of metastatic melanoma. Methods: We studied 66 stage IV, resected melanoma patients followed at Mayo Clinic from 2000 to 2010. Log rank chi-square analysis was used to determine the best cut-off values for each pre-operative variable, while proportional hazards models were used to compared survival. Results: The median follow-up of the cohort was 24 months (range: 2.3 – 117 months). ALC-PO, AMC-PO and ALC/AMC-PO, as continuous variables, were all identified as prognostic factors for both relapse-free survival (RFS) and overall survival (OS). The best cut-off values for ALC-PO, AMC-PO and ALC/AMC-PO were 1.9; 0.62; and 2.05, respectively. Using Kaplan-Meier analysis, patients with an ALC-PO ≥ 1.9 x 109/L experienced superior OS and RFS compared with ALC-PO < 1.9 x 109/L patients [median OS of 58 months vs. 34 months, p < 0.04; median RFS of 14 months vs. 5 months, p < 0.009]. Conversely, a low AMC-PO (<0.62 x 109/L) was associated with better OS and RFS compared with higher AMC-PO (≥ 0.62 x 109/L): [median OS of 47 months vs. 14 months, p < 0.007; median RFS of 9 months vs. 5 months, p < 0.02]. When the ALC-PO and AMC-PO were combined as an ALC/AMC ratio, the group with an ALC/AMC-PO ≥ 2.05 experienced a superior OS and RFS compared to patients with ALC/AMC-PO < 2.05: [median OS of 49 months vs. 12 months, p < 0.0001; median RFS of 10 months vs. 4 months, p < 0.0001]. Multivariate analysis showed ALC/AMC-PO to be an independent prognostic factor for RFS and OS (HR = 0.32, p < 0.003; HR = 0.23, p < 0.002). Conclusions: Our study showed, that ALC/AMC-PO ratio is an independent prognostic factor for RFS and OS in patients undergoing resection of metastatic (stage IV) melanoma.
Phase III evaluation of American ginseng (panax quinquefolius) to improve cancer-related fatigue: NCCTG trial N07C2.
Authors: Barton Debra L. , Liu Heshan , Dakhil Shaker R. , Linquist Breanna M. , Sloan Jeff A. , Nichols Craig R. , McGinn Travis W. , Balcueva Ernie P. , Seeger Grant R. , Loprinzi Charles L.
Published: March 2020

9001

Background: Ginseng is popularly used as a treatment for fatigue, one of the most common and disabling symptoms in people diagnosed with cancer. It is termed an “adaptogen”, thought to help the body combat negative effects of stress. This trial was to evaluate 2,000 mg American Ginseng versus placebo for cancer-related fatigue (CRF). Methods: Patients with cancer undergoing or having completed curative intent treatment and experiencing fatigue, rated at least 4 on a numeric analogue fatigue scale (1-10) for ≥1 month, were eligible. Exclusion criteria included CNS lymphoma, brain malignancies, or prior use of ginseng or chronic systemic steroids. Other etiologies for fatigue, such as pain and sleep, were also excluded. Patients were randomized to receive, in a double blind manner, 2,000 mg/d of American Ginseng or placebo in BID dosing for 8 weeks. The primary endpoint was change from baseline in the general subscale of the Multidimensional Fatigue Symptom Inventory (MFSI) at 4 weeks. Other MFSI subscales and the fatigue-inertia subscale of the Profile of Mood States (POMS) were also analyzed. Data were transformed to a 0-100 scale. Results: 364 patients were enrolled from 10/2008 to 07/2011. Data at 4 and 8 weeks are provided for several fatigue endpoints in the table below; higher numbers are better. Mental, emotional and vigor subscales of the MFSI were not significantly different between arms. There were no statistically significant differences in any grade of toxicity or self reported side effects between ginseng and placebo. Conclusions: This trial provides data to support that American Ginseng reduces general and physical CRF over 8 weeks without side effects. The treatment did not provide significant reductions in fatigue at 4 weeks and did not impact mental, emotional, and vigor dimensions of fatigue. [Table: see text]
Long-term protective effects of the angiotensin receptor blocker telmisartan on epirubicin-induced inflammation, oxidative stress, and myocardial dysfunction.
Authors: Mantovani Giovanni , Dessi' Mariele , Piras Alessandra , Madeddu Clelia , Orgiano Laura , Cadeddu Christian , Antoni Giorgia , Mercuro Giuseppe
Published: March 2020

9006

Background: Chronic inflammation, oxidative stress and renin-angiotensin system (RAS) play a significant role in chemotherapy-induced cardiotoxicity (CTX). Telmisartan (TEL), an antagonist of the angiotensin II type-1 receptor, reduces anthracycline (ANT)-induced CTX. Methods: A phase II placebo (PLA)-controlled randomized trial was carried out to assess the role of TEL in the prevention of cardiac subclinical damage induced by epirubicin (EPI). Forty-nine patients (mean age ± SD, 53.0±8 years), cardiovascular disease-free with cancer at different sites and eligible for EPI-based treatment, were randomized to one of two arms: TEL n=25; PLA n=24. A conventional echocardiography equipped with Tissue Doppler imaging, strain and strain rate (SR) was performed, and serum levels of proinflammatory cytokines, IL-6 and TNF-α, and oxidative stress parameters, reactive oxygen species (ROS) and glutathione peroxidase were assessed. All assessments were carried out at baseline, after every 100 mg/m2 EPI dose and at 6, 12 and 18-month follow-up (FU). Results: A significant reduction in the SR peak in both arms was observed at t2 (cumulative dose of 200 mg/m2 EPI) in comparison to t0. Conversely, at t3, t4 (300, 400 mg/m2 EPI), 6, 12 and 18-month FU, the SR increased reaching the normal range only in TEL arm, while in PLA arm SR remained significantly lower as compared to t0. The differences between SR changes in PLA and TEL arms were significant from 300 mg/m2 EPI (t3) up to 18 month-FU. IL-6 increased significantly in PLA arm at t2 compared to t0, but remained unchanged in the TEL arm. ROS levels also increased significantly at t2 vs. baseline in PLA arm, while remained unchanged in TEL arm. The mean change in ROS and IL-6 at t2 was significantly different between the two arms. At 3, 6, 12 and 18 month-FU, ROS and IL-6 decreased in comparison to t2 in PLA arm, while remained low in TEL arm. Conclusions: Our results suggest that TEL is able to reverse acute EPI-induced myocardial dysfunction and maintain a normal systolic function up to 18 month-FU. These effects are likely due to two different mechanisms, RAS blockade and prevention of chronic inflammation/oxidative stress.
Electronic self-report assessment for cancer: Results of a multisite randomized trial.
Authors: Berry Donna Lynn , Hong Fangxin , Halpenny Barbara , Wang Qian , Partridge Ann H. , Fann Jesse R , Wolpin Seth , Lober William B , Bush Nigel , Bosco Jaclyn Lee Fong , Parvathaneni Upendra , Amtmann Dagmar , Back Anthony
Published: March 2020

9008

Background: Attending to symptoms and side effects promotes safe and effective delivery of cancer therapies. Providing focus to the patient’s report in the clinic can efficiently address the most important concerns, without extending visit times. The web-based electronic self report assessment for cancer (ESRA-C) and clinician summary has been shown to improve patient-clinician communication about symptoms and quality of life issues (SQI). The purpose of this trial was to evaluate the impact of an enhanced ESRA-C intervention (ESRA-C INT) on symptom outcomes. Methods: Patients (planned N=702) with all cancer types treated in stem cell transplant, medical oncology and radiation oncology at two comprehensive cancer centers used ESRA-C to self-report SQI during and after new anti-cancer therapy, with summary reports delivered to clinicians. Patients were randomized to standard ESRA-C (control) or ESRA-C INT adding the opportunity to self-monitor SQI between clinic visits and receive self-care SQI management education, plus custom coaching on how to report SQI to clinicians, all delivered via a secure web sites. We analyzed the intervention effect on Symptom Distress Scale (SDS) scores using a two-sided t-test and multivariate linear regression, adjusting for pre-selected covariates, including baseline SDS, age, service, and work status. Results: Among 757 patients (increased N due to involuntary attrition), demographic variables were balanced between groups except age (t=2.13; p=.03) with a younger INT group (mean 1.97 year difference). Of the 562 patients who completed final reports, the control group reported significantly higher SDS scores (t= 1.98; p = .048). A significant interaction between study group and age was observed; significantly lower SDS scores were found in the ESRA-C INT group among patients > 50 years (-1.95; p=.002), and no significant difference among patients < 50. Conclusions: Adding self-care and communication coaching to ESRA-C, a system to allow self-report and clinician notification of SQI, reduced symptom distress in a large sample of patients during and after active cancer treatment compared with ESRA-C alone. Patients over the age of 50, in particular, may benefit from the intervention.
Curcumin for radiation dermatitis: A randomized, double-blind, placebo-controlled clinical trial of 30 breast cancer patients.
Authors: Ryan Julie L. , Heckler Charles E , Ling Marilyn N , Williams Jacqueline P , Pentland Alice P , Morrow Gary R.
Published: March 2020

9027

Background: Radiation dermatitis occurs in approximately 95% of patients receiving radiation therapy for cancer and often leads to pain and treatment delays. There is no standard treatment with demonstrated effectiveness for the prevention of radiation dermatitis. We conducted a randomized, double-blind, placebo-control clinical trial to assess the efficacy of curcumin, a potent antioxidant and anti-inflammatory component of turmeric, to reduce radiation dermatitis in 30 breast cancer patients. Methods: Eligible patients included adult females with non-inflammatory breast cancer or carcinoma in situ prescribed radiation therapy without concurrent chemotherapy. After randomization, patients took four 500 mg capsules of curcumin or placebo three times daily throughout their course of radiation therapy (total daily dose = 6.0 g). Weekly assessments included Radiation Dermatitis Severity (RDS) Score, presence/absence of moist desquamation, erythema measure, and McGill Pain and Symptom Inventory (SI) questionnaires. Results: The 30 evaluable patients were white (90%; mean age = 58.1 years) with ER+PR+ breast cancer (76.7%) who did not have total mastectomy (90%) or chemotherapy prior to start of radiation therapy (56.7%). No significant differences were observed between arms for demographics, compliance, erythema, pain, symptoms, or radiation skin dose. Standard pooled variances t-test showed that curcumin reduced RDS at end of treatment compared to placebo (mean RDS = 2.6 vs 3.4; p=0.008). Fisher’s exact test showed that curcumin significantly reduced the presence of moist desquamation at the end of radiation therapy (28.6% vs. 87.5 %; p=0.002). Repeated measures analysis confirmed divergence of RDS between curcumin and placebo arms at Week 5. Conclusions: Oral curcumin, 6.0 g daily during radiation therapy, reduced radiation dermatitis severity and moist desquamation in breast cancer patients. A multisite CCOP trial (N=700) is underway to confirm the effectiveness of curcumin to reduce radiation dermatitis severity during various radiation therapy regimens for breast cancer. Support: IND 75,444, Dermatology Foundation, KL2 RR024136, NCI PHS 1R25CA10618.
Social environment as a predictor of smoking cessation and recidivism in lung cancer survivors.
Authors: Eng Lawson , Su Jie , Palepu Prakruthi R. , Hon Henrique , Fadhel Ehab , Harland Luke , La Delfa Anthony , Habbous Steven , Kashigar Aidin , Cuffe Sinead , Leighl Natasha B. , Pierre Andrew , Goldstein David P. , Liu Geoffrey , Xu Wei
Published: March 2020

9032

Background: Smoking during cancer treatment negatively impacts treatment, survival and quality of life. Lung cancer patients with a smoking history often continue to smoke; some ex-smokers re-start after diagnosis. Social environment impacts cessation and recidivism rates in non-cancer patients. We assessed whether the same influences occur among lung cancer patients. Methods: Lung cancer patients, recruited from Princess Margaret Hospital, completed a baseline questionnaire about their demographics and smoking history (at diagnosis). A follow-up questionnaire was administered at a median of two years, assessing changes in smoking habits, exposure at home/work/among friends, healthcare use, social support and alcohol use since diagnosis. The relationship between each variable with cessation/recidivism was analyzed. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. Results: 478 patients completed both questionnaires. Of the 100 current smokers at diagnosis; 52 quit by the time of the follow-up questionnaire. Among 294 ex-smokers, 15 started to smoke after diagnosis. None of the 84 never smokers at baseline started to smoke after diagnosis. Exposure to smoking at home was associated with continued smoking and relapse (OR=5.1, 95% CI: 1.8–14.3, p=0.001; and OR=3.9, 95% CI: 0.8–14.4, p=0.04, respectively). Specifically, spousal smoking was associated with both continued smoking (OR=7.3, 95% CI: 2.4–21.7, p=2.0E-04) and recidivism (OR=3.7, 95% CI: 0.6–16.6, p=0.08). Having more than a few friends who smoke is associated with continued smoking (OR=3.5, 95% CI: 1.4–8.7, p=0.005) and relapse (OR=4.8, 95% CI: 1.5–15.0, p=0.004). Not completing high school was also associated with continued smoking (OR=3.0, 95% CI: 1.2–7.6, p=0.02). Multivariate analysis identified spousal smoking as the major single predictor of continued smoking (OR=8.8, 95% CI: 2.2–34.8, p=0.002). Conclusions: Smoking cessation programs for lung cancer patients should not only target the patient but also include the immediate family, consider a patient’s peers and be tailored to the patient’s education level. Involvement of the immediate family and consideration of peers may help prevent smoking relapse.
Patient information desire in actual decision making for advanced cancer treatment: Do doctors know their patients?
Authors: Oostendorp Linda JM , Ottevanger Petronella B , Van Der Graaf Winette T.A. , Stalmeier Peep FM
Published: March 2020

9036

Background: Providing information is an important element of cancer care. While several studies have investigated patients' information desire, to our knowledge, this study is the first to involve patients facing an actual decision. We examined the information desire of patients at the point of decision making, the ability of doctors to judge this desire, and the information provided by the doctor. Methods: This prospective multicenter study included patients with advanced colorectal or breast cancer faced with the decision whether or not to pursue second-line chemotherapy. Patients received the usual treatment-related information from the doctor plus a decision aid from a nurse. The aid contained information on adverse events, tumor response, and survival. For each item, the nurse asked the patient whether the information was desired and whether it had been disclosed by the doctor and the doctor made a substitute judgment of the patient’s information desire on the inclusion form. The match between patient’s desire and doctor’s judgment was expressed in percentage agreement and agreement corrected for chance (κ). Results: By 01/2012, 71 patients had received the decision aid. Median age was 62 years (range 39-80), 38% were male, and 28% had college education or higher. Information on adverse events, tumor response, and survival was desired by 94%, 90%, and 73% of patients. The doctors judged that information desire would be 100%, 97%, and 81%, respectively. There was a poor match between doctor’s judgment and actual information desire for adverse events (94%, κ not applicable), tumor response (87%, κ = -0.049), and survival (61%, κ = -0.104). When asked whether the information was previously disclosed by the doctor, 73%, 57%, and 30% of patients answered affirmatively. Conclusions: Patients expressed a high information desire, which was accurately judged by the doctors. However, doctors were unable to judge an individual patient’s information desire beyond chance. According to the patients, doctors did not disclose all desired information, especially on survival. Decision aids, similar to those used here, have been shown to help doctors provide safe, effective, and timely information to patients.
Patient-reported satisfaction with reconstructed breasts in the long-term survivorship period: Comparison of autologous and nonautologous breast reconstruction.
Authors: Scott Amie , Ho Adelyn , Klassen Anne , Cano Stefan , VanLaeken Nancy , Cordeiro Peter , Pusic Andrea
Published: March 2020

9043

Background: Breast cancer patients undergoing mastectomy may choose to have reconstruction performed using either their own tissue or an implant. As many patients are candidates for both, valid and reliable patient-centered outcomes data are crucial to shared medical decision-making. The objective of this study is to determine whether patient-reported satisfaction with their reconstructed breasts is dependent on type of reconstructive surgery and length of time from reconstruction. Methods: Participants were recruited from Memorial Sloan-Kettering Cancer, NY and the University of British Columbia, Canada. Patients completed the BREAST-Q, a new patient-reported outcome measure for breast surgery patients. The dependent variable was the BREAST-Q Satisfaction with Breast score, a 16-item scale scored from 0-100. Procedure type, time since surgery, and patient characteristics were independent variables. Univariate analysis and clinical judgment were used to identify variables included in the model, and multivariate linear regression models were constructed to control for confounders. Results: The study sample consisted of 510 women (response rate 62%). The sample was on average aged 54.3 ± 9.3 (range 21-81), surveyed 3.71 years ± 1.55 (range 1-9) after surgery, 66% were reconstructed using an implant. Type of surgery and laterality were found to be variables that predicted higher patient satisfaction with their breasts after controlling for radiation therapy, follow-up time, timing of surgery, age, body mass index, and major complications (surgery type p<0.001; laterality p<0.001, R-square=0.17). Conclusions: As there is a growing population of breast cancer survivors, understanding how a woman’s satisfaction with her reconstructed breasts changes over time is essential. This study suggests that patient satisfaction with breast reconstruction depends on the type of reconstruction a woman undergoes. This patient-centered outcome data can be used to enhance shared medical decision-making by providing patients with information about realistic expectations for satisfaction with breasts related to type of surgery chosen.
Predictors of satisfaction with decision in patients with advanced cancer.
Authors: Hitz Felicitas , Klingbiel Dirk , Ribi Karin , Li Qiyu , Cerny Thomas , Koeberle Dieter
Published: March 2020

9045

Background: Treatment decisions in palliative cancer care depend on various patient-, treatment, and disease-related factors. This study investigated patients’ satisfaction with decision and decision-making preferences in a Swiss oncology network and evaluated factors that predict satisfaction with decision (SWD). Methods: Patients receiving a new line of palliative cancer treatment completed a multi-dimensional questionnaire 4-6 weeks after treatment decision. Patient-reports comprised socio-demographic information, satisfaction with decision (primary endpoint), subjective treatment goal, preferences for decision-making, health, locus of control, and several quality of life (QoL) domains. Information on diagnosis, line of therapy, metastases, prognosis, performance status and duration of consultation were provided by the attending physician. Predictors of SWD (range: 0=worst; 30=best) were evaluated by uni- and multivariate (primary analysis, 80% power, 5% significance level) regression models. We consider ≥24 points as high SWD. Results: 445 out of 480 patients treated in 8 hospitals and 2 private practices completed all questions regarding the primary endpoint. 44% of patients preferred shared-, 42% physician-centered decision making. Median duration of consultation was 30 minutes (range 10-200 minutes). Overall, 326 (73%) patients reported high SWD. In univariate analyses various factors (e.g. global and physical QoL, performance status, treatment goal, locus of control, prognosis and duration of consultation) were significant predictors of SWD. The only significant predictor in the multivariate analysis was duration of consultation, which was positively associated with SWD (p=0.01). Conclusions: SWD is generally high in patients with advanced cancer treated in an oncology network in Switzerland. Our results indicate that duration of consultation is a very important factor among many others in predicting SWD. In busy clinical practice, taking your time with patients may be a simple measure to enhance patients’ SWD.
Mistletoe as complementary treatment in patients with advanced non-small cell lung cancer treated with carboplatin-based combinations: A randomized phase II study.
Authors: Bar-Sela Gil , Wollner Mira , Hammer Liat , Agbarya Abed , Dudnik Elizabeth , Haim Nissim
Published: March 2020

9052

Background: The mistletoe preparation, iscador, is commonly used in complementary medicine for improving the quality of life (QoL) of cancer patients, but its efficacy needs to be further proved. This randomized phase II study was aimed at assessing the value of iscador as a modifier of chemotherapy-induced toxicity in chemotherapy-naïve non-small-cell lung cancer (NSCLC) patients treated with carboplatin containing regimens. Methods: Patients with stage IIIA or IIIB/IV NSCLC, ECOG performance status 0-2, and no history of brain metastasis were randomized to receive either chemotherapy alone (arm-1) or chemotherapy plus iscador Q 10mg SC injections 3 times weekly until tumor progression (arm-2). Chemotherapy consisted of 21-day cycles of IV carboplatin area under curve 5.0, day 1, combined with IV gemcitabine 1000mg/m2, days 1, 8, or with IV pemetrexed 500mg/m2, day 1. Results: Seventy-two patients were enrolled, 39 to arm-1 and 33 to arm-2. The arms were well balanced except that more patients with PS-0 were in arm-1 (p=0.041). Most patients (65%) were in stage IV and 62% had squamous histology. Median overall survival was 11 months in both arms. Median TTP was 4.8 months (arm-1) and 6 months (arm-2) (p=0.07). Carboplatin dose reductions and delays in gemcitabine on day 8 were more frequent in arm-1 (44% vs. 13% in arm-2, p<0.005; 31% vs. 13% in arm-2, p< 0.013). The difference in grade 3-4 hematological toxicity was not significant. More non-hematological toxicity was observed in arm-1 (41% compared to 16% in arm-2, p=0.043). The number of hospitalizations was higher in arm-1, 54%, compared to 24% in arm-2 (p=0.016). No significant difference was seen in QoL using the EORTC QLQ-C30 questionnaire; However, significant improvement in arm-2 was seen in coughing (p=0.013) and peripheral neuropathy (p=0.019). Conclusions: Chemotherapy dose reductions, severe non-hematological side effects, and hospitalizations were less frequent in patients treated with iscador. Further investigation of iscador as a modifier of chemotherapy-related toxicity is warranted.
Prospective survey study regarding the implementation of new communication skills curriculum for medical oncology trainees.
Authors: Shumway Nathan M. , Struble Erika J.
Published: March 2020

9058

Background: After a diagnosis of cancer, many patients suffer from anxiety and distress from uncertainty of symptoms, treatments, and prognosis. Clinicians must recognize opportunities to explore concerns. This study assesses oncology trainees’ views about communication with cancer patients before (PRE) and after (POST) a 12 month curriculum. Methods: Medical oncology fellows were surveyed PRE and POST a communication curriculum consisting of case studies and 6 core lectures which included fundamentals, breaking bad news, transitions to palliative care, advanced care planning, conducting family conferences, and discussing treatment options and informed consent. A 5 point Likert-scale was used to measure fellows’ attitudes and comfort regarding communication PRE and POST with questions grouped according to core topics. (≤2 = trainee disagreement, 3=neutral opinion, and ≥ 4 indicated agreement). Results: PRE and POST surveys were completed by 11 and 8 trainees respectively. In PRE 100% felt communication skills were important and 63% believed these skills could be taught. 82% felt there was not enough time during most visits to address emotion. This decreased to 27% in POST. 18% PRE agreed they were comfortable recognizing coping mechanisms versus 100% POST. 45% felt comfortable eliciting values in PRE versus 87.5% POST. Only 1 fellow (9%) felt comfortable addressing futility in PRE versus 25% in POST. The median grouped score for fundamentals increased from 15 to 17 (p=0.016) and median grouped score for advance care plans and DNR increased from 11 to 13(p=0.026). Conclusions: There is a need to improve oncology communication skills. Our curriculum is just one approach. After intervention, the majority of fellows agreed there was enough time to address emotion and felt more comfortable recognizing coping mechanisms and eliciting values. Discussing futility remains difficult for our fellows. All fellows were more comfortable with fundamental communication skills and advance care plans after the curriculum. The extent the curriculum contributed to the change in survey results is unclear. Further research is needed to guide communication education of oncologists.
The use of olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy.
Authors: Navari Rudolph M. , Nagy Cindy K , Gray Sarah E
Published: March 2020

9064

Background: Olanzapine (OLN) has been shown to be a safe and effective agent for the prevention of CINV. OLN may also be an effective rescue medication for patients who develop breakthrough CINV despite having received guideline directed CINV prophylaxis. Methods: A double blind, randomized phase III trial was performed for the treatment of breakthrough CINV in chemotherapy naïve patients receiving highly emetogenic chemotherapy (HEC) (cisplatin, >70 mg/m2, or doxorubicin, >50 mg/m2 and cyclophosphamide, > 600mg/m2 ) comparing OLN to Metoclopramide (METO). Patients who developed breakthrough emesis or nausea despite prophylactic dexamethasone (12 mg IV), palonosetron (0.25 mg IV), and fosaprepitant (150 mg IV) pre chemotherapy and dexamethasone (8 mg p.o. daily, days 2-4) post chemotherapy were randomized to receive OLN, 10 mg orally daily for three days or METO, 10 mg orally TID for three days. Patients were monitored for emesis and nausea for the 72 hours after taking OLN or METO. Eighty patients (median age 56 yrs, range 38-79; 43 females; ECOG PS 0,1) consented to the protocol and all were evaluable. Results: During the 72 hour observation period, 30 of 42 (71%) patients receiving OLN had no emesis compared to 12 of 38 (32%) patients with no emesis for patients receiving METO (p<0.01). Patients without nausea (0, scale 0-10, M.D. Anderson Symptom Inventory) during the 72 hour observation period was: OLN: 67% (28 of 42); METO 24% (9 of 38) (p<0.01). There were no Grade 3 or 4 toxicities. Conclusions: OLN was significantly better than METO in the control of breakthrough emesis and nausea in patients receiving HEC.
Humoral and cellular immune response after influenza vaccination in patients with postcancer fatigue and patients with chronic fatigue syndrome.
Authors: Prinsen Hetty , de Vries Jolanda , Stelma Foekje , Mulder Sasja , Van Herpen Carla , Leer Jan Willem , Elving Lammy , Bleijenberg Gijs , Van Laarhoven Hanneke W.M.
Published: March 2020

9070

Background: Postcancer fatigue (PCF) is a frequently occurring problem, impairing quality of life. Patients with chronic fatigue syndrome (CFS) also suffer from severe fatigue symptoms. We hypothesized that in fatigued patients (PCF and CFS) alterations in immune response could explain fatigue symptoms. Therefore, we examined whether the humoral and/or cellular immune response after influenza vaccination differed between fatigued patients and non-fatigued individuals and between PCF and CFS patients. Methods: PCF (n=15) and CFS patients (n=22) were vaccinated against influenza. Age and gender matched non-fatigued cancer survivors (n=12) and healthy controls (n=23) were included for comparison. Antibody responses were measured at baseline and at day 21 by a hemagglutination inhibition test. T cell responses were measured at baseline and at day 7 by a lymphocyte proliferation and activation assay. Results: Both patient groups developed seroprotection rates comparable to the accompanying control groups. Functional T cell reactivity was observed in all groups. Proliferation at baseline was significantly lower in fatigued patients compared to non-fatigued individuals. A significant increase in proliferation from baseline to day 7 was observed in fatigued patients, but not in controls. At day 7, proliferation was not significantly different between fatigued patients and non-fatigued individuals. CD4+CD127-FoxP3+ expression was significantly higher in PCF patients compared to non-fatigued cancer survivors. Conclusions: We observed a lower T cell proliferation at baseline in fatigued patients compared to non-fatigued individuals, suggesting a difference in the baseline state of the immune system between fatigued patients and non-fatigued individuals. Furthermore, the difference in CD4+CD127-FoxP3+ expression between PCF and CFS patients suggests subtle differences in immune state between these two fatigued patient groups. However, since humoral and cellular immune responses after vaccination did not differ significantly between fatigued patients and non-fatigued individuals, vaccination of fatigued patients (PCF and CFS) can be effective.
Inflammatory markers and symptom burden in patients with multiple myeloma undergoing autologous stem cell transplantation.
Authors: Williams Loretta A. , Wang Xin Shelley , Johnson Valen E. , Liu Ping , Shah Nina , Mendoza Tito R. , Reuben James M. , Cohen Evan N. , Gilmore Katherine R. , Ilagan Venus M , Cleeland Charles S.
Published: March 2020

9081

Background: We explored the association between activation of inflammatory networks and development of severe symptoms during mobilization and the acute phase of autologous hematopoietic stem cell transplantation (ASCT) for multiple myeloma (MM). Methods: From mobilization through the first 3 months after ASCT, multiple symptoms were measured repeatedly via the myeloma module of the M. D. Anderson Symptom Inventory (MDASI-MM). Serum levels of interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-a, soluble TNF receptors 1 and 2 (sTNF-R1, sTNF-R2), IL-1 receptor antagonist (IL-1RA), vascular endothelial growth factor (VEGF), macrophage inflammatory protein-1 (MIP-1a), monocyte chemoattractant protein (MCP)-1 and C-reactive protein (CRP) were collected up to 11 times per patient and assayed by Luminex. Ordinal regression modeling was used to analyze repeated-measures data. Results: Among50 MM patients, the most severe symptoms reported by werefatigue, pain, muscle weakness, disturbed sleep, drowsiness, numbness, poor appetite, and bone aches. Symptoms worsened rapidly from conditioning therapy and peaked at WBC nadir. Over time, controlling for age, sex, and MM stage, increased serum IL-6 (P=.0007) and MCP-1 (P=.0005) were significantly associated with worsening of the most severe symptoms; MIP-1a (P=.005) and VEGF (P=.002) were inversely associated with these symptoms. Increased CRP was significantly associated with worsening pain (P=.01), fatigue (P=.007), and bone aches (P=.006). Conclusions: This longitudinal study indicates a strong association between dynamic changes in circulating inflammatory molecules and the most severe symptoms in MM patients during the acute phase of ASCT. This observation, similar to IL-6-related multisymptom development around WBC nadir of allogeneic SCT (Wang et al, 2008), provides evidence of potential inflammation-induced behavioral changes in humans. Testing of anti-inflammatory interventions is warranted to further confirm the role of inflammation in the development of symptoms and identify effective mechanism-driven symptom management during ASCT.
Gender difference in vulnerability and geriatric syndromes among elderly cancer survivors.
Authors: Fan Lin , Noyes Katia , Zhang Ning , Fiscella Kevin , Mohile Supriya Gupta
Published: March 2020

9091

Background: Few studies have evaluated the gender difference of vulnerability and geriatric syndromes (GS) among cancer survivors. Methods: Using 2003 Medicare Current Beneficiary Survey, we applied multivariable logistic regression to evaluate the association of gender with vulnerability and GS among cancer survivors. Vulnerability is measured by Vulnerable Elders Survey-13 (VES-13), which is calculated from age, self-rated health status, difficulty with physical activities and functional activities. Vulnerability is defined by a VES-13 score of 3 or higher. 8 common geriatric syndromes were assessed: sight trouble, hearing trouble, nutrition problem, incontinence, falls, depression, memory loss and osteoporosis. Cancer survivors are defined as patients with cancer diagnosed more than one year ago. Results: Among the 1,883 cancer survivors, 749 (40.0%) were male; 1,134 (60.0%) were female. Female survivors had a higher prevalence of vulnerability (47.8% vs 35.7%), and GS (65.5% vs 44.6%) than male survivors. Mean GS number was 1.19 for female survivors, while 0.77 for male survivors (p<0.001). More specifically, female survivors had significantly higher prevalence of sight trouble (7.73% vs 5.0%), incontinence (14.3% vs 7.1%), falls (28.9% vs 22.1%), depression (13.8% vs 7.7%) and osteoporosis (38.2% vs 6.7%). After adjusting for confounders, female survivors were more likely to be vulnerable (adjusted OR (AOR): 1.62; CI: 1.21-2.17; p=0.001); have a geriatric syndrome (AOR: 2.39; CI: 1.91-3.00; p<0.001); have sight trouble (AOR: 1.70; CI: 1.00-2.87; p=0.049); have incontinence (AOR: 2.48; CI: 1.67-3.69; p<0.001); have depression (AOR: 1.87; CI: 1.29-2.71; p<0.001); and have osteoporosis (AOR: 8.48; CI: 6.07-11.84; p<0.001). Conclusions: Female cancer survivors experience a higher prevalence of vulnerability and overall geriatric syndromes.
Medical oncologist’s commitment in the end of life (EoL) care of cancer patients: The caregiver's perspective.
Authors: Bascioni Romeo , Giorgi Francesca , Esperide Barbara , Basirat Farnoosh , Borriello Maria Rosaria , Brugni Manuela , Scriboni Sonia , Rastelli Francesca , Appignanesi Remo , Picciotti Giovanna , De Signoribus Giorgio , Giustini Lucio
Published: March 2020

9098

Background: Optimizing the impact of EoL care on cancer patients (pts) and their caregivers should be a primary goal of an oncology unit. In this study we evaluated satisfaction of family caregivers when the medical oncology team assisted pts until death. Methods: Two oncology units were reorganized to ensure continuity of care; oncologists trained in palliative care medicine assisted pts until EoL. The model assumes that the medical oncologist (MO) is the physician in charge throughout the entire disease trajectory. Relatives of pts assisted at home or at an inpatient hospice underwent a semistructured phone interview conducted by a psychologist or a social worker > 1 month after pts' death. Satisfaction was evaluated for symptoms control, communication, psychological support, overall quality of care and continuity of therapeutic relationship with the MO. A final open-ended question was included for any additional comment. Satisfaction was measured using a five-point Likert scale ranging from very dissatisfied to very satisfied and converted to a 0-to-100 scale. Results: Relatives of 65 pts were contacted, 55 accepted the interview (27 spouses, 22 sons, 5 in-laws, 1 parent); 50/55 were the leader caregiver. Patients were followed at home (41) or at an inpatient hospice (14), for 1-24 wks. Satisfaction mean scores were: symptoms control 76/100, communication 85, psychological support 82 and overall quality of care 87; a specific question on the relevance of the MO in EoL care produced a score of 87, with no negative or neutral responses recorded for this item. Of note, a common perception among caregivers was the appreciation of the MO's commitment during EoL in addition to the technical quality of the intervention. The overall satisfaction score was higher than in our previous study in which a continuity of care model was not formally adopted, with a score improvement from 55 to 87/100. Conclusions: A care pathway where the MO is involved in EoL management of cancer pts improved satisfaction of caregivers.When a longstanding and trusting relationship has been established, the pts-MO connection should not be lost to prevent feelings of abandonment.
Comparative patient-centered outcomes (health state and adverse sexual symptoms) between adjuvant brachytherapy versus no adjuvant brachytherapy in early-stage endometrial cancer.
Authors: Damast Shari , Alektiar Kaled M. , Goldfarb Shari Beth , Gerber Naamit Kurshan , Eaton Anne , Patil Sujata , Mosenkis Jeffrey , Sit Laura , Rogak Lauren J. , Leitao Mario M. , Carter Jeanne , Basch Ethan M.
Published: March 2020

9104

Background: We performed a cross-sectional analysis of survivors of stage I endometrial cancer (EC) to examine the relationship between receipt of adjuvant intra-vaginal radiation therapy (IVRT), health state (HS), and sexual functioning (SF). Methods: Survivors were administered anonymous questionnaires containing demographic and treatment-related items, the EQ5D to measure current HS, and the Female Sexual Function Index (FSFI) to measure current SF. All were disease-free and had undergone simple hysterectomy (SH) with or without adjuvant IVRT at least one year prior to questionnaire completion. None had received chemotherapy or hormonal therapy. The study was IRB-approved under a waiver of consent. The primary endpoint was a comparison of EQ5D-health states and FSFI scores between survivors who had received SH alone and those who had received SH and adjuvant IVRT. Fisher’s exact test was used to compare IVRT and no-IVRT groups and multivariate regression was applied to find associations between factors and the outcome measures. Results: 136 (66.3%) participants had undergone SH alone and 69 (33.7%) had undergone SH and adjuvant IVRT. The SH alone group was younger; otherwise, the two groups were balanced with respect to ethnicity, marital status, education level, medical co-morbidities (diabetes, hypertension, anxiety), type of SH (laparotomy vs minimally invasive surgery-MIS), and baseline sexual activity. In the IVRT and no-IVRT groups, the median EQ5D-health states were 88 (range 40-100) and 85 (range 10-100) respectively, and the median FSFI scores were 14.1 (range 1.2-35.4) and 16.5 (range 1.2-34.8) respectively. Controlling for age and type of SH, receipt of IVRT was associated with better HS (p=0.018) and not associated with poorer SF (p=0.1399). Receipt of laparotomy (vs MIS) was associated with poorer HS and worse SF (p=0.0156 and p=0.0115, respectively), and its detrimental effect on FSFI score was more pronounced in the IVRT compared to no-IVRT group (p=0.0486). Conclusions: Compared to SH alone, receipt of adjuvant IVRT was generally not associated with poorer SF or HS.
A randomized trial of a cardiopulmonary resuscitation (CPR) video (V) in advance care planning (ACP) for progressive hepatopancreaticobiliary cancer patients.
Authors: Epstein Andrew S. , Volandes Angelo E. , Gary Kristen , Chen Ling Y. , Li Yuelin , Agre Pat , Levin Tomer , Reidy Diane Lauren , Meng Raymond D. , Segal Neil Howard , Yu Kenneth H. , Janjigian Yelena Yuriy , Abou-Alfa Ghassan K. , Kelsen David Paul , O'Reilly Eileen Mary
Published: March 2020

9105

Background: CPR is an important advance directive topic in patients with progressive cancer; however such discussions are challenging. Previous work by Volandes et al suggests that V images help, however whether V educational information about CPR engenders broader ACP discourse is unknown. Methods: A randomized trial of an educational V or narrative (N) in patients with progressive hepatopancreaticobiliary cancers was conducted. The V and N were 3 minutes long and contained an identical description of CPR. Primary endpoint: ACP documentation 1-month post-test (either a formal advance directive or a documented ACP discussion), 80% powered with 0.01 type-I error rate for estimated advance directive completion rates of 70% V arm vs. 25% N arm with a sample of 56 subjects. Secondary endpoints (exploratory): impressions of the study information; pre and post knowledge of and preferences for CPR and mechanical ventilation; and follow-up longitudinally (to death or 6 months post-test). Results: 56 subjects consented and analyzed. 1-month post-test ACP documentation was not significantly higher in the V arm (12/30, 40.0%) vs. the N arm (4/26, 15.4%); Fisher’s exact test, OR = 3.583 [95% CI: 0.886 – 17.937], p = 0.07. Knowledge increased in both arms after the intervention. Preferences for CPR changed in V arm but not in N arm; for mechanical ventilation, there was no change in either arm. The majority of subjects in both arms reported the information as helpful, comfortable to discuss, and recommended to others. Longitudinally, outcomes were similar between V & N arms, respectively: % advance directives completed (63% & 58%); median days from test to advance directive (60 & 72) and advance directive to death (21 & 20); median ACP documentation after 1 month (0 & 1); median hospital admissions (1 & 1), days of stay (5 & 7), ICU stays (0 & 3) and CPR/mechanical ventilation (1 & 3). 52% of all subjects died by study end, the majority in hospice care. Conclusions: This first randomized trial addressing downstream ACP effects of V vs. N decision tools demonstrated a trend towards more ACP documentation in V patients. Further research into these types of educational media is needed.