bluuebunny/crossref_metadata_2025 huggingface dataset:
Methylphenidate (MP) and nursing telephone intervention (NTI) for cancer-related fatigue (CRF) in advanced cancer patients: A double-blind randomized phase II trial.
Authors: Bruera Eduardo , Yennurajalingam Sriram , Perez-Cruz Pedro Emilio , Hui David , Frisbee-Hume Susan , Allo Julio , Palmer J. Lynn
Published: March 2020

9023

Background: CRF is the most common and distressing symptom in advanced cancer patients. Preliminary studies support MP and NTI for CRF (Bruera et al. JCO 2006). The primary objective of our study was to determine the effect of MP as compared to placebo (P). A secondary objective was to investigate the role of NTI as compared to control telephone intervention (CTI). Methods: Advanced cancer patients with fatigue ≥4/10 on the Edmonton Symptom Assessment Scale (ESAS), normal cognition, no evidence of major depression and hemoglobin ≥8 were eligible. Patients were randomized to 4 groups in a 2x2 factorial design (MP+NTI, P+NTI, MP+CTI and P+CTI). Primary endpoint was Functional Assessment of Chronic Illness-Fatigue (FACIT-F) subscale scores between day 15 and baseline. The dose and duration of methylphenidate was 5 mg every two hours, as needed, up to 20 mg/day. We tested the median difference in FACIT-F subscale scores between the groups using the Kruskal Wallis test and Wilcoxon signed rank test. Longitudinal regression analysis was conducted with a mixed model. Results: Total accrual was 197. Mean (SD) age was 58 (12), female 67% (N=148), white 72% (N=136), gastrointestinal cancers were the most common 22% (N=41). Baseline FACIT-F subscores were similar among the 4 groups. The median FACIT-F subscores showed significant improvement between Day 15 and baseline for all four groups except for P+CTI (Table): MP+NTI (4.5, P=0.004), P+NTI (8, P<0.001), MP+CTI (7, P<0.001), and P+CTI (5, P=0.06), with no statistically significant difference between MP and P (6 vs. 6, P=0.89). Longitudinal regression analysis showed a time effect (P<0.001) and group differences for NTI vs. CTI with FACIT-F (P=0.13) and ESAS (P=0.03). Grade 3 toxicities were similar between the MP and P arms (34/93 vs. 24/97, P=0.09). Conclusions: MP was not effective as compared to P for CRF in advanced cancer patients. NTI may be effective and should be further studied. [Table: see text]
Effect of cancer cachexia on treatment toxicity in metastatic colorectal cancer patients: Results of a prospective multicenter study.
Authors: Barret Maximilien , Dalban Cecile , Taïeb Julien , Malka David , Mansourbakht Touraj , Latko Ewa , Antoun Sami
Published: March 2020

9026^

Background: Malnutrition reduces tolerance to treatment and survival in numerous cancers, including metastatic colorectal cancer (mCRC). Previous studies have shown that chemotherapy toxicity may be linked to sarcopenia. We evaluated the effect of sarcopenia on chemotherapy toxicity among mCRC patients. Methods: In this prospective, cross-sectional, multicenter study, oncological and nutritional data were collected in all consecutive mCRC patients between March 7th and March 20th 2005 in three hospitals. Computed tomography (CT) images were analysed using Slice-O-Matic software V4.3 (Tomovision) to evaluate cross-sectional areas (cm2) of muscle tissue (MT), visceral and subcutaneous adipose tissue (VAT and SAT). The 3rd lumbar vertebra (L3) was chosen as a reference, since L3 and whole-body measurements are linearly related. Indexed on height, MT, VAT and SAT (cm2/m2), were computed and described, after stratification on sex. In accord with the literature, sarcopenia was defined as MT <55 cm2/m2 for men and <39 cm2/m2 for women. Images were obtained within one month of clinical evaluation. Toxicities were evaluated according to the NCI-CTC, version 3.0, in the two months following clinical evaluation. Results: 53 mCRC patients (72% men (M)), participated in the study. According to body mass index (BMI) only 7% of female patients (F) and 3% M were malnourished (BMI<17 kg/m²), and 93% F and 97% M were of normal weight or overweight (BMI> 25kg/m²). These results are to be compared to the 38% (F) and 82% (M) of patients with sarcopenia. Grade 3-4 toxicities were observed in 28% of the cases, with neurotoxicity in 6%, diarrhea 2%, anemia 2%, neutropenia 9%, and nausea and vomiting 6%. In multivariate analysis including age, sex, BMI, sarcopenia, SAT and VAT, the only factor associated with grade 3-4 toxicity was sarcopenia (OR= 13.55 95% CI [1.08;169.31], p=0.043). Conclusions: In mCRC patients undergoing chemotherapy, low muscle tissue was much more frequently observed (68%) than “visible” malnutrition (4%). Despite the small number of patients included in our study, we showed that sarcopenia was associated with severe chemotherapy toxicity in mCRC.
A randomized controlled trial of expressive writing for patients with renal cell carcinoma (RCC).
Authors: Burnight Timothy , Wood Christopher G. , Tannir Nizar M. , Jonasch Eric , Pisters Louis L. , Matin Surena F. , Spelman Amy , Wei Qi , Cohen Lorenzo
Published: March 2020

9029

Background: Most previous research examining the efficacy of brief expressive writing interventions have used small sample sizes and followed people for no more than 3 months. We conducted a large randomized trial to examine an expressive writing intervention for patients with renal cell carcinoma and followed them for 10 months after the end of the writing sessions. Methods: Two hundred patients with RCC were randomly assigned to either write their deepest thoughts and feelings about their cancer (EW) or to write about neutral topics (NW) on four separate occasions over 10 days for a maximum of 20 minutes at each writing session. Patients completed the MD Anderson Symptom Inventory (MDASI), Brief Fatigue Inventory, SF-36, IES, CES-D, and PSQI at baseline and then again 1, 4, and 10 months after the writing sessions. Results: The mean age of the participants was 58 (range 34-82 years), 41% were women, and staging data were 39% stage I, 15% stage II, 19% stage III, and 27% stage IV. The groups were well balanced on all demographic and medical characteristics. Examination of group differences 1 month after the writing sessions, controlling for the respective baseline measure, revealed decreased IES scores for the EW group (intrusive thoughts: EW, 5.0 v NW, 7.2; p<.02; avoidance behaviors: EW, 6.3 v NW, 8.7; p<.07). By 4 months after the intervention, the EW group reported higher levels of SF-36 Social Functioning scores (EW: 52.6 v NW: 49.7; p<.04). At the 10 month time point, the EW group reported fewer cancer-related symptoms (EW: 20.8 v NW: 30.8; p<.04), higher levels of SF-36 Role Physical scores (EW: 69.6 v NW: 54.0; p<.02), and fewer sleep disturbances (subscale of the PSQI; EW: 1.4 v NW: 1.6; p<.05). Means for the other SF-36 subscales at 10 months were in the expected, but did not reach statistical significance. There were no group differences for CES-D or fatigue scores at any time point. Mediation analyses revealed that IES scores at 1 month mediated the effects of EW on cancer-related symptoms (F= 1.85, p<.06) at the 10 month follow up. Conclusions: These findings indicate expressive writing leads to short-term reduction in intrusive thoughts about the cancer experience and results in long-term improvement in aspects of quality of life.
Strength and endurance training in the treatment of lung cancer patients staged IIIA/IIIB/IV.
Authors: Henke Corinna C. , Cabri Jan , Fricke Lothar , Pankow Wulf , Kandilakis Giannis , Feyer Petra C. , De Wit Maike
Published: March 2020

9033

Background: This RCT tested the effect of a specially designed strength and endurance training on the independence in activities of daily living and quality of life in lung cancer patients staged IIIA/IIIB/IV while receiving palliative chemotherapy. The aim was to break the vicious circle created through the connection of physical inactivity and the worsening of symptoms and side effects. Methods: Between August 2010 and December 2011 lung cancer patients staged IIIA/IIIB/IV with a good performance status receiving an inpatient palliative chemotherapy treatment at the Vivantes Hospital Neukölln/Berlin, were randomized into an intervention and control group. The Barthel Index and the EORTC QLQ-C30/ LC13 questionnaire were used for evaluation. The Six-Minute-Walk-Test and stair walking in combination with the Modified Borg Scale have been used to test the patient’s endurance capacity. Furthermore muscle strength was examined. Non-parametrical data were statistically analyzed with the Wilcoxon and Mann-Whitney-U test. For parametric data student t- tests were used. A significance level of p< .05 was accepted. Results: Out of 46 patients, who signed the informed consent, 29 patients completed the trial (18= Intervention group, 11= Control group). Significant differences between the groups were detectable in the Barthel Index (IGmean(SD)=92.08 (15.15); CGmean=81.67 (14.98); p=.041), and in single scores of the EORTC QLQ C-30/LC-13 questionnaire (Physical Functioning p=.025; Haemoptysis p=.019, Pain in Arms or Shoulder p=.048, Peripheral Neuropathy p=.050, Cognitive functioning p=.050). Significant differences were found between the groups concerning the 6MWT, stair walking and strength capacity (IG>CG). Additionally the level of dyspnoea decreased significantly in the IG while performing submaximal walking activities. Conclusions: The training program has a positive impact on the patient’s independence in carrying out activities of daily living. Although it does not have a significant impact on the patient’s quality of life, single factors can be significantly improved. Moreover it has a positive effect on the patient’s endurance and strength capacity. The dyspnoea perception is improved.
Factors associated with life expectancy (LE) < 3 months (mo) among older adults receiving palliative chemotherapy (chemo).
Authors: Hurria Arti , Hardt Molly , Tew William P. , Mohile Supriya Gupta , Owusu Cynthia , Gross Cary P. , Gajra Ajeet , Lichtman Stuart M. , Katheria Vani , Ramani Rupal , Zavala Laura , Klepin Heidi D. ,   on behalf of the Cancer and Aging Research Group (CARG)
Published: March 2020

9034

Background: Optimal treatment decision-making for older adults with advanced cancer requires a better understanding of risk factors associated with limited LE. Our objective was to evaluate the factors associated with LE< 3mo among patients (pts) age > 65 who were beginning a new chemo regimen. Methods: We conducted a secondary analysis of a multi-site cohort study of pts ≥65 years receiving chemo (Hurria et al, JCO 2011). This analysis included only pts receiving palliative chemo. Bivariate analysis and multivariate logistic regression were utilized to identify factors associated with LE < 3 mo including: sociodemographics, labs [hemoglobin (Hb), albumin, liver function, creatinine clearance], and geriatric assessment (GA) variables (functional status, social support, comorbidity, psychological, cognitive, and nutritional status). Results: Among 290 pts (median age 72 [range 65-91], 52% female) with advanced cancer (gastrointestinal 28%, lung 31%, breast/gyn 22%, other 19%), 13.4% died within 3 mo of chemo initiation. In bivariate analysis, pts with LE < 3mo were more likely (p<0.05 for each variable) to have lower albumin and Hb, unintentional weight loss, and poorer physical function [defined as need for assistance with instrumental activities of daily living (IADL), lower score on Medical Outcomes Survey (MOS) Physical Health, MD-rated and patient-rated Karnofsky performance status (KPS), and MOS Social Activity score]. Measures of functional status were highly correlated with one another and therefore one functional status measure (in addition to measures significant in bivariate analysis) was included in each multivariate logistic regression. In multivariate analyses, (controlling for age, comorbidity, and line of chemo) poorer physical function (as evaluated by need for assistance with IADLs, MOS Physical <70, or MD-rated KPS <70) and unintentional weight loss were independently associated with LE<3mo (p<0.05). Conclusions: Among older pts with advanced cancer who were prescribed a new chemo regimen for palliative intent, physical function measures (as evaluated by geriatric assessment and MD report) and unintentional weight loss were associated with LE < 3months.
The influence of age plus standard clinical approach with or without comprehensive geriatric assessment (CGA) on treatment decisions in older cancer patients: Final results.
Authors: Decoster Lore , Kenis Cindy , Van Puyvelde Katrien , De Greve Jacques , Conings Godelieve , Knapen Marie Claire , Lobelle Jean Pierre , Milisen Koen , Vanorle Katrien , Flamaing Johan , Wildiers Hans
Published: March 2020

9035

Background: The aim of this prospective study was to examine how age and standard clinical approach with and without CGA results determine treatment decisions in older cancer patients (pts). Methods: This study,conducted in 2 Belgian university hospitals, included pts ≥ 70 years with a malignant tumor (breast, colorectal, ovarian, lung, prostate and hematological) if a new cancer therapy was considered. All pts underwent a uniform CGA. Results were communicated to the treating physician. After the treatment decision, an interview with the treating physician was performed, using a predefined questionnaire: 1/ What would be your oncological treatment proposal in case the pt was 55y without other comorbidity? 2/ Is this different from your treatment proposal for this pt according to age and standard clinical approach without CGA results? 3/ Is this different from your treatment proposal for this pt with CGA results? Results: From October 2009 till July 2011, 937 pts were included in the study. Median age was 76y (range 70-95) and 63.5% was female. A total of 902 (96.3%) questionnaires were completed and 56.2% of the physicians were aware of the CGA results at treatment decision. In 381 pts (42.2%; 95%CI 39.0-45.5) age and standard clinical approach led to a different treatment decision compared to younger pts without comorbidity. This influence was most prominent for chemotherapy decisions: 309 patients did not receive standard chemotherapy (reduced dose (13), less toxic regimen (163), less toxic regimen at reduced dose (5) or no chemotherapy (128)). When the physician was aware of the CGA, these results influenced their treatment in 6.7% (95%CI: 4.5-8.9), mostly concerning chemotherapy. In 8 pts CGA results encouraged the treating physician to choose a more aggressive chemotherapy regimen and in 11 pts CGA results led to a decision of palliative care. Conclusions: Based on this prospective trial, we conclude that physicians use adapted treatment regimens in older versus younger pts, only based on age and standard clinical approach. CGA results change the treatment decision in 6.7% and sometimes trigger the use of a more aggressive treatment.
In-hospital cancer care: Are we missing an opportunity for end of life care?
Authors: Rocque Gabrielle Betty , Barnett Anne Elizabeth , Illig Lisa , Bailey Howard Harry , Campbell Toby Christopher , Stewart James A. , Cleary James F.
Published: March 2020

9039

Background: Little data exists on the estimated survival of patients with metastatic cancer after hospitalization. As part of a prospective quality improvement project, we characterized the population of patients admitted to an inpatient oncology service in an academic medical center with emphasis on the disposition at discharge and overall survival. Methods: We collected data over a 4 month period (9/1/10-12/23/10) representing 149 admissions of 119 unique patients. We measured patient characteristics, disease evaluation, procedures, consults, imaging studies performed, disposition, length of stay, and overall survival. These data were compared to a similar study conducted in our center in 2000. Results: Uncontrolled symptoms were the most common reason for admission (pain 28%, dyspnea 9%, nausea 9%). Imaging studies were more common than in 2000 (415 vs. 196 total procedures). Eighty-five percent of patients had progressive disease. Seventy percent of patients were discharged home without additional services such as home health or hospice. The overall median survival was poor in 2000 and in 2010, 100 days and 60 days from discharge, respectively. Despite an overall poor prognosis, palliative care consultation was obtained only 13 times (8% of admissions) and 18% of patients were enrolled in hospice at discharge. Conclusions: An unscheduled hospital admission portends a poor prognosis. Cancer patients in the hospital are nearing the end-of-life with a median life expectancy of approximately 3 months and could be considered hospice-eligible and appropriate for a palliative care consult. We believe that hospital admission represents a missed opportunity to provide palliative care services and end-of-life counseling to this patient population.
Pulmonary symptoms and their importance to patients with non-small cell lung cancer undergoing second- and third-line chemotherapy.
Authors: Magasi Susan , Kaiser Karen , Mallick Rajiv , Cella David
Published: March 2020

9056

Background: As new cancer therapies are developed, it is important to evaluate their efficacy based not only on survival outcomes but also meaningful patient benefit in terms of symptoms and concerns that are important to patients. The purpose of this study of patients undergoing 2nd/3rd line chemotherapy for non-small cell lung cancer (NSCLC) was to characterize pulmonary symptoms and the importance patients place on these symptoms, as a part of assessing the content validity of the Pulmonary Symptom Index (PSI) of the Functional Assessment of Cancer Therapy – Lung (FACT-L). Methods: We conducted semi-structured thematic interviews with 20 stage III/IV NSCLC patients undergoing 2nd or 3rd line treatment. Interviews included open elicitation of NSCLC symptoms and their functional impact, and participant ratings of the relative importance of pulmonary symptoms. Results: Mean age was 62 years (range 30-79); 80% had non-squamous histology, and 30% had co-morbid COPD. While participants described a range of symptom experiences and severity, a core set of pulmonary symptoms emerged - shortness of breath (reported by 16/20, 13/20 rated as very important), cough (reported by 14/20, 10/20 rated as very important), and chest tightness (reported by 15/20, 9/20 rated as very important); these matched key symptoms in the PSI. Symptom importance ratings were influenced by the functional impact they had upon patient ability to perform valued roles and responsibilities. Patients described diverse coping strategies including breaking down activities into manageable tasks, priority setting, physical assistance, emotional support, and health promoting changes in diet and exercise. Ninety percent (18/20) of participants reported tiredness or fatigue; most said it was “very important.” A quarter (5/20) of the participants reported having no pulmonary symptoms. Conclusions: These results in NSCLC patients undergoing 2nd/3rd line treatment support the importance, relevance, and impact of core pulmonary symptoms included in the PSI and offer initial evidence that its content may constitute a key element of patient benefit in evaluating the efficacy of new cancer therapies.
Pharmacokinetics, pharmacodynamics, and tolerability of BCD-017, a novel pegylated filgrastim: Results of open-label controlled phase I study with dose escalation in healthy volunteers.
Authors: Nikitin Kirill D. , Fitilev Sergei B. , Chernovskaya Tatiana V. , Rudenko Elena G. , Vozzhaev Alexander V. , Titarova Yulia Y , Yakushev Vadim A. , Ivanov Roman A.
Published: March 2020

9060

Background: Pegfilgrastim (conjugate of filgrastim and 20 kDa PEG) is approved for treatment of chemotherapy-associated neutropenia. BCD-017 is a covalent conjugate of filgrastim with 30 kDa PEG. Increased molecular weight of PEG molecule may provide additional benefits compared to pegfilgrastim. We have conducted this open-label phase I study to assess the PK, PD and tolerability of BCD-017. Methods: 24 healthy male volunteers signed the informed consent and were sequentially assigned to receive 1, 3 or 9 mg of BCD-017 or 5 mcg/kg/day of filgrastim for 7 days, 6 volunteers per group. Outcome measures included absolute neutrophil count (ANC) and СD34+ cell count, PK parameters and adverse events (AEs). Results: BCD-017 induced a fast and significant increase of ANC. Median maximum ANC (ANCmax) for BCD-017 1, 3, 9 mg and filgrastim was 18.68 (10.62-21.02), 25.92 (15.43-28.07), 32.22 (18.22-45.79), and 28.21 (21-31.95) ×103 cells/mm3, respectively; median time to ANCmax was 24 (12-24); 48 (24-72); 72 (48-72); and 132,5 (12-169) h, respectively; median increase in СD34+ cells number 96 h post dose was 4.7 (1.2-6.5), 6.5 (1.7-12.3), 40.9 (24.5-102), and 17.8 (3.3-35.2) times, respectively. Filgrastim serum concentration was analyzed using ELISA. Median Cmax for BCD-017 3 and 9 mg and filgrastim was 45 (31-65), 446 (191-649), and 40 (20-54) ng/mL, respectively; median Tmax was 48 (24-72), 36 (24-48), and 8 (6-8) h respectively; median T1/2 was 65 (51-70), 46 (41-57), and 6.7 (6.2-7.6) h, respectively. BCD-017 was well tolerated. No dose-limiting AEs were observed. AEs included headache, back pain, myalgia, arthralgia, thrombocytopenia, hyperuricemia, alkaline phosphatase/LDH increased. All AEs were of grade 1-2. Compared to filgrastim, the best tolerability was observed in 3 mg group. Conclusions: BCD-017 is shown to be a potent stimulator of granulopoiesis. BCD-017 3 mg did not differ from filgrastim in terms of ANC increase and its safety was shown in healthy volunteers. Further phase II study of BCD-017 for treatment and prophylaxis of neutropenia in patients receiving cytotoxic chemotherapy is necessary.
Interdisciplinary palliative care in metastatic non-small-cell lung cancer.
Authors: Koczywas Marianna , Cristea Mihaela C. , Reckamp Karen L. , Thomas Jay , Sun Virginia , Ferrell Betty R.
Published: March 2020

9068

Background: Palliative cancer care is the integration into cancer care of therapies that address multiple issues that cause suffering for patients and their families and impact their life quality. Challenges and barriers continue to hinder the integration of palliative care into comprehensive, ambulatory oncology care. This paper aims to describe how symptoms, distress, and quality of life (QOL) data from the usual care phase of a NCI-supported Program Project (P01) informed the development of an interdisciplinary palliative care intervention for patients with metastatic non-small-cell lung cancer (NSCLC). Methods: Patients receiving usual care for metastatic NSCLC were recruited into this prospective longitudinal study. A total of 130 patients with stage IV NSCLC were accrued, and 114 patients had evaluable data. Upon informed consent, patients completed outcome measures that assessed physical function/cognitive status, social activities and support, symptom characteristics, psychological distress, and overall QOL. Patient-reported outcomes were completed at baseline, 6, 12, and 24 weeks post-accrual. Results: Subjects were primarily female (64%), ranged in age from 40-84 years, and 39% were ethnic minorities. The majority were former smokers (66%). KPS, IADL, and Cognitive scores deteriorated significantly over time (p=.001, .009, and .042, respectively). Patients reported higher severity scores with symptoms such as dyspnea, fatigue, insomnia, lack of appetite, peripheral neuropathy, pain, dry skin, nail changes, and problems with sexual interest in all four time periods. Global Symptom Distress Index and Total Symptom score both significantly worsened at 24 weeks (p=.003 and .017, respectively). Physical Well-Being worsened significantly (p=.036), while overall QOL, spiritual well-being, and psychological distress scores remained statistically stable over time. Conclusions: Patients with metastatic NSCLC continue to experience high symptom burden and diminished physical well-being over time while receiving treatments. An interdisciplinary palliative care intervention is currently being tested to improve symptom burden and overall QOL.
Psychological impact of exercise in women with breast cancer receiving adjuvant therapy: What is the optimal dose needed?
Authors: Carayol Marion , Bernard Paquito , Boiche Julie , Riou Francois , Mercier Betty , Cousson-Gelie Florence , Romain Ahmed Jerome , Ninot Gregory
Published: March 2020

9074

Background: Several meta-analyses have examined the role of exercise interventions in improving psychological outcomes in cancer survivors but most did not focus on adjuvant therapy period and did not investigate the optimal dose of exercise needed. Methods: The present meta-analysis examines the impact of exercise interventions delivered at this particular period on fatigue, anxiety, depression and quality-of-life (QoL) as well as dose-response relationships between volume of prescribed exercise and these psychological outcomes. Randomized controlled trials that proposed an exercise intervention to breast cancer patients undergoing chemotherapy and/or radiotherapy were systematically identified and coded. Standardized mean differences (SMDs) of psychological outcomes were weighted by the inverse of their variances to obtain a pooled estimate using random effects model. Linear and quadratic regressions were carried out to explore dose-response relationships. Results: In total, 17 studies involving 1380 participants and 20 exercise interventions were included. Intervention subjects significantly reduced their fatigue and depression levels showing pooled effect sizes (EF) and their associated 95% confidence interval (95%CI) of -0.28 [95%CI: -0.54; -0.03] and -0.28 [95%CI: -0.46; -0.09] respectively. Levels of anxiety also appeared to be reduced but pooled estimate did not reach significance (p=0.06). Significantly increased QoL was observed: EF=0.34 [95%CI: 0.07; 0.62] favouring intervention. Consistent and significant inverse associations of weekly and total volume of prescribed exercise were observed with fatigue (F test: p=0.04, R²=0.19 and p=0.009, R²=0.26 respectively) and QoL (F test: p=0.01, R²=0.14 and p=0.02, R²=0.29 respectively), implying that SMDs magnitude decreased as exercise dose increased. Conclusions: Exercise intervention enhanced fatigue, depression and QoL in breast cancer patients undergoing adjuvant therapy. Prescription of relatively low doses of exercise (<12 MET.h per week) consisting in approximately 90-120 min of weekly moderate physical exercise seems more efficacious in improving fatigue and QoL than higher doses.
Effect of aprepitant on adherence to high-dose cisplatin-based chemotherapy.
Authors: Makarenko Serge , Cheung Winson Y.
Published: March 2020

9078

Background: Treatment of locally advanced head and neck cancers (HNC) and gastroesophageal cancers (GEC) frequently consists of high-dose cisplatin, which is highly emetogenic. Our aims were to 1) explore the impact of aprepitant for improving adherence to cisplatin-based chemotherapy in HNC and GEC, 2) examine its effect on reducing chemotherapy-induced nausea and vomiting (CINV) and 3) determine if use of aprepitant changed after introduction of insurance coverage for this drug. Methods: Patients diagnosed with HNC or GEC in British Columbia, Canada from Jan 2008 and June 2011 and prescribed high-dose cisplatin were reviewed. Using regression models that adjusted for confounders, we evaluated the relationship between aprepitant use and treatment and outcome characteristics, such as number of chemotherapy cycles, prevalence of CINV, and recurrence and survival. Results: A total of 333 patients were identified: 162 HNC and 171 GEC patients of whom 80% were men, 44% were aged >/=60 years, 35% were smokers, and 42% were alcohol users. Aprepitant was prescribed in 49%, nausea and vomiting occurred in 64 and 24%, respectively, and completion of all planned cisplatin was 52%. Younger patients (55 vs 41%, p=0.01) and those with less tumor burden (64 vs 38%, p<0.01) were more likely to be given aprepitant. Individuals who received aprepitant were significantly less likely to experience CINV (p<0.01). Use of aprepitant differed between HNC and GEC patients (p<0.01); however, its use did not increase when insurance coverage of this agent was introduced (p=0.16). In multivariate analyses, aprepitant use was significantly associated with adherence to all planned cisplatin treatments (OR 2.33, 95% CI 1.27-4.25, p<0.01). In Cox regression, completion of all cisplatin cycles was significantly correlated with a lower risk of recurrence (HR 0.56, 95%CI 0.32-0.97 p=0.04) and a trend towards decreased death (HR 0.56, 95%CI 0.31-1.10, p=0.10). Conclusions: Aprepitant was associated with a reduction in CINV in both HNC and GEC patients and correlated with better adherence to high-dose cisplatin-based chemotherapy. Individuals who completed all planned cisplatin had improved outcomes, specifically a lower risk of recurrence from HNC and GEC.
Baseline subclinical sensory deficits and the development of pain and numbness in patients with multiple myeloma (MM) being treated with chemotherapy.
Authors: Vichaya Elisabeth G. , Wang Xin Shelley , Boyette-Davis Jessica A. , He Zijing , Thomas Sheeba K. , Shah Nina , Mendoza Tito R. , Williams Loretta A. , Cleeland Charles S. , Dougherty Patrick M.
Published: March 2020

9082

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity experienced by patients with MM. Patients may develop painful and non-painful (e.g., numbness) symptoms that impair function and often persist after therapy is terminated. This study examined the predictive value of baseline subclinical sensory deficits on the development of treatment-related pain and numbness. Methods: Patients (N=56) who had two or fewer cycles of induction therapy and no obvious neuropathy were assessed for sensory deficits using quantitative sensory testing (QST). Patients reported the severity of pain and numbness (on a 0-10 scale) at least weekly via the MD Anderson Symptom Inventory during induction (up to 16 weeks); 15 of 56 patients provided data for up to 16 additional weeks of maintenance therapy. These values correlate to patient reported pain and numbness in the hands/feet. Based on data collected from healthy controls, patients were classified as being with or without a sensory deficit at baseline on each QST domain. We fit linear mixed models for pain and numbness with each sensory deficit and time, controlling for cumulative cycles, diabetes, age, and treatment agent. Data is shown as mean ± standard deviation. Results: Patients who showed baseline deficits in sharpness detection (20%) reported significantly lower levels of pain (1.2±1.9 vs 3.1±2.9, p=.004) and numbness (0.4±0.8 vs 2.4±2.6, p<.001) during induction therapy and less numbness (0.0 vs 3.5±2.8, p=.001) during maintenance therapy. Further, those who showed deficits in warmth detection (40%) reported higher levels of pain (5.2±2.8 vs 1.7±2.3, p<.001) and numbness (5.8±2.2 vs 1.6±1.8, p<.001) during maintenance therapy. Finally, those with lower skin temperature (47%) reported higher levels of pain (4.5±2.3 vs 1.7±2.9, p=.005) during maintenance therapy. Conclusions: Our results suggest that subclinical sensory deficits may be useful in determining a patient’s risk for developing CIPN prior to initiation of induction therapy. This information could be used to provide patients with more-personalized chemotherapy plans that take into account their neuropathy risk.
A randomized trial to determine if vitamin B6 can prevent hand and foot syndrome in cancer patients treated with capecitabine chemotherapy.
Authors: Braik Tareq , Yim Barbara , Evans Arthur T , Kassem Mohammed Azher , Phillips Tycel Jovelle , Mullane Michael Russell , Lad Thomas E. , Hussein Lily , Cleveland Barbara , McDunn Susan H.
Published: March 2020

9085

Background: Capecitabine is an oral fluoropyrimidine that is used to treat various malignancies. Hand and Foot Syndrome (HFS) is a dose limiting toxicity of capecitabine and can limit the use of this agent in some patients. Some investigators have observed that pyridoxine (vitamin B6) can ameliorate HFS caused by capecitabine. We designed a prospective trial to determine if pyridoxine can prevent HFS in patients receiving capecitabine. Methods: In our double-blind, placebo controlled trial, we randomly assigned eligible patients treated with capecitabine to receive either daily pyridoxine 100 mg or placebo along with their capecitabine-containing chemotherapy regimen. Patients were observed during the first four cycles of capecitabine treatment. The primary end point was the incidence and grade of HFS that occurred in both arms. Results: Between 2008 and 2011, 77 patients were randomly assigned to receive either pyridoxine (n=38) or placebo (n=39). Both arms were matched in baseline characteristics. The median age was 53.5 years. The ethnic composition of the study population was African American 53%, Caucasian 22%, Hispanic 18%, and Asian 7%. The daily doses of capecitabine were: 2000 mg/m2 (69 pts), 1650 mg/m2 (5 pts), 1400 mg/m2 (2 pts) and 1000 mg/m2 (1 pt). Dosages of capecitabine were equally matched between the two arms of the study. HFS occurred after a median of 2 chemotherapy cycles in both groups. HFS developed in 10/38 (26%) patients in the pyridoxine group and in 8/39 (20%) patients in the placebo group (p=0.547). Therefore, the risk of HFS was 6 percentage points higher in pyridoxine group (95% CI for difference: -13 percentage points to +25 percentage points). Given our study results, we can be confident of excluding a true benefit from pyridoxine larger than 13 percentage points. No difference in HFS grades was observed. Conclusions: Prophylactic pyridoxine (vitamin B6), given concomitantly with capecitabine-containing chemotherapy, was not effective for the prevention of HFS. [Table: see text]
Risk of rash with nilotinib: A systematic review of the literature and meta-analysis.
Authors: Drucker Aaron Mark , Wu Shenhong , Berman Ellin , Lacouture Mario E.
Published: March 2020

9088

Background: Nilotinib is indicated for the treatment of chronic myelogenous leukemia (CML). The reported incidence and risk of rash from this medication vary widely and have been inconsistently reported in published trials. Therefore we conducted a systematic review and meta-analysis of the literature to determine the incidence and risk of developing rash. Methods: Relevant studies were identified from the PubMed database (1998-2012), abstracts presented at ASCO and ASH Conferences (2004-2011) and Web of Science database (1998-2012). Eligible studies were limited to prospective Phase II-III clinical trials in which patients received nilotinib at doses of either 300 mg or 400 mg twice daily. Incidence, relative risk (RR), and 95% confidence intervals (CI) were calculated using random-effects or fixed-effects models based on heterogeneity of included studies. Results: Data from a total of 3,186 patients receiving nilotinib in 16 clinical trials were available for analysis. The overall incidence of all-grade and high-grade (grade ≥3) rash were 33.1% (95% CI: 27.7-39.1) and 2.6% (95% CI: 2.1-3.4), respectively. Incidence of all-grade rash for patients with CML, gastrointestinal stromal tumor (GIST) and systemic mastocytosis were 33.2% (95% CI: 27.2-39.9), 25.7% (95% CI: 14.0-42.5) and 25.0% (95% CI: 15.7-37.4), respectively. Nilotinib was associated with increased risk of all-grade rash (RR=2.891, 95% CI: 2.079-4.020; P<0.001) when compared to patients treated with imatinib. Risk of high-grade rash was increased compared to imatinib (RR=1.823, 95% CI: 0.670-4.957), but this was not statistically significant (P=0.24). Conclusions: Patients with hematologic malignancies and GIST who are treated with nilotinib are at significant risk for developing a rash. Further studies for characterization, prevention and treatment of this untoward toxicity are needed in order to maintain patients’ quality of life and minimize the need for dose modification, which may impact clinical outcome.
The chemotherapy-induced peripheral neuropathy (CIPN) outcome measure standardization (CI-PeriNomS) study: From consensus to validity and reliability in CIPN assessment.
Authors: Cavaletti Guido ,   CI-Perinoms Study Group
Published: March 2020

9089

Background: Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a debilitating and dose limiting complication of cancer treatment. However, the impact of CIPN has never been studied in a clinimetric manner, in its impact on quality of life. This study was performed to select appropriate outcome measures and to establish, for the first time with a clinimetric approach, their validity and reproducibility. Methods: After literature review and a consensus meeting, face/content validity were obtained for the following scales: the National Cancer Institute Common-Toxicity-Criteria (NCI-CTC), the Total Neuropathy Score (TNSc), the modified INCAT sensory sumscore (mISS), the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and CIPN20 quality of life measures. 281 patients with stable CIPN were examined through an EU/US collaboration involving 20 oncology/neurology centers. For each scale the inter- and intra-rater agreement was evaluated by means of weighted K-Cohen coefficients and 95% confidence intervals, when analyzing qualitative ordinal scales and by means of Spearman's rank correlation coefficient and t-test when analyzing quantitative ordinal scales. The adopted weights for the estimate of K-Cohen coefficients were the Fleiss-Cohen weights. For validity purposes, the Kruskal-Wallis equality-of-populations rank test was performed relating the mISS and TNSc to the NCI-CTC grades. Results: Proper, although slightly different, inter-/intra-observer scores (i.e. r > 0.7) were obtained for the TNSc, mISS, and NCI-CTC sensory/motor subscales. Test-retest values were also high for the EORTC QLQ-C30 and for the recently developed and never formally tested CIPN20. Acceptable validity scores were obtained through correlation between the the mISS and TNSc to the NCI-CTC scores (p values ranging from 0.04 to < 0.001). Conclusions: Proper validity and reliability scores were demonstrated for the set of selected outcome measures in CIPN. These results will allow to base new trials on a solid methodological background, although future studies are warranted to investigate the responsiveness issues.
Predicting length of survival for adult, outpatient oncology patients using clinic visit data.
Authors: Brown Laura E. , Decker Brian , Decker David A.
Published: March 2020

9095

Background: The ability to predict a patient’s length of survival (LOS) has the potential to become an extremely valuable tool to aid in patient care, treatment, and end-of-life decisions made by the patient, their clinician, and extended support network. Methods: This preliminary study constructed models to predict LOS. Data from 10,667 patients was collected in an Electronic Medical Record over two years with LOS determined by matching records with the Social Security Death Index. The patient information available to construct the models consisted of basic patient demographics (single-entry information: e.g., age, cancer diagnosis, cancer stage, gender), transcriptions of physicians’ notes (to mine for other factors), and laboratory values (time-series or time-stamped information: e.g., weight, blood pressure, hemoglobin, creatinine, medication and treatments administered, etc.). A 5-fold nested cross-validation experimental design was used to train (using several possible representations of the data), test, and compare least-squares and support vector regression (SVR) models. Evaluations based on standard error are reported. Results: Linear, polynomial (up to 4th degree), and radial basis kernels were considered for SVR with the best model selected as the 2nd order polynomial. Preliminary results show that the best linear least-squares model is able to predict LOS with a standard error of +/- 34 days. The best support vector regression model has a slightly better prediction performance with standard error of +/- 32 days. Conclusions: This preliminary research shows the feasibility of predicting LOS from outpatient, clinical data. Further work is planned to improve the model performance, test other models, and determine which clinical indicators in oncology are most important for accurate predictions.
Clinical trial participation as part of end-of-life (EOL) cancer care: Associations with medical care near death and bereaved caregivers’ mental health.
Authors: Phelps Andrea Catherine , Zhang Baohui , Prigerson Holly Gwen
Published: March 2020

9102

Background: Clinical trial participation is necessary to improve existing therapies, encouraged by national guidelines, and common among advanced cancer patients. The relationships between trial participation and important EOL outcomes such as aggressive care are unknown. Methods: Coping with Cancer Study, an NCI-funded multicenter prospective cohort study of advanced cancer patients and their caregivers, enrolled September 2002 – February 2008. Patients were interviewed at baseline, and clinical trial participation was documented by chart review. Patients were followed to death, (median 4.4 months from baseline). Medical care and quality of life (QOL) in the last week of life was assessed by caregiver interview and chart review. Caregiver interview 6 months post-bereavement assessed QOL and mental health (Structured Clinical Interview for the DSM-IV). The primary outcome was aggressive EOL care (ventilation, resuscitation, or chemotherapy in the last week of life). Secondary outcomes were bereaved caregivers’ mental health and QOL. Propensity-score weighting balanced patient characteristics (e.g. clinical variables, EOL preferences) that differed by trial participation. Propensity-score weighted regression models estimated the effect of trial participation on outcomes. Results: Of 246 patients followed to death with non-missing propensity scores, 27 were clinical trial participants. In propensity-score weighted analyses, trial participation was significantly associated with aggressive EOL care [29.6% v 9.1%; adjusted OR (AOR), 12.14; 95% CI, 3.65-40.36], ICU admission, mechanical ventilation, chemotherapy, and a trend toward inferior QOL near death (p = 0.069). Of 180 matched caregivers, trial participation predicted less mental illness [AOR, 0.15; 95% CI 0.04-0.57], major depression [AOR, 0.25; 95% CI, 0.08-0.80], but was unassociated with QOL (p = 0.15) in adjusted analyses. Conclusions: Clinical trial participation is associated with increased risk of aggressive EOL care for advanced cancer patients, but better mental health for bereaved caregivers.
Understanding the symptom experience of breast cancer outpatients: The validity and utility of the M.D. Anderson Symptom Inventory (MDASI).
Authors: Mendoza Tito R. , Zhao Fengmin , Cleeland Charles S. , Wagner Lynne I. , Patrick-Miller Linda J. , Fisch Michael
Published: March 2020

9106

Background: Breast cancer and its treatments can produce multiple symptoms that cause distress and impair function. The MDASI, a patient-reported outcome measure of symptoms (sxs) and functional interference has been validated in general oncology and has the potential to inform symptom experience and guide treatment specific to breast cancer patients (pts). Methods: The Eastern Cooperative Oncology Group (ECOG) conducted the Symptom Outcomes and Practice Patterns (SOAPP) study at academic and community medical oncology clinics and included pts with breast cancer of all stages and phases of care. At baseline and 4 weeks, pts completed the MDASI. Symptom experiences and psychometric properties of the MDASI in breast cancer pts (n = 1544) were analyzed. Results: The median age was 58 years, and the race/ethnicity included 11% black and 8% hispanic. 5% had ECOG performance status (PS) ≥2. The 5 most prevalent moderate/severe sxs reported at baseline were fatigue (31%), disturbed sleep (27%), drowsiness (21%), hair loss (22%) and dry mouth (19%); moderate/severe skin rash (6%) and vomiting (4%) were the least prevalent. At follow-up, about 1/3 of patients had moderate/severe fatigue and 19% had moderate/severe pain and distress. Internal consistency and test-retest reliability were good, with Cronbach alphas of ≥0.85 and intraclass correlations of ≥0.76 for all subscales. Among those whose PS was stable or improving, the change scores in sx severity improved most for sleep disturbance, numbness/tingling, and difficulty remembering things. Significantly higher scores and moderately large effects for the severity scale were reported by pts with poorer PS (ES=.61) and those with local/regional/metastatic disease (ES=.67). Results were similar for the interference scale. Pts whose quality of life (QOL) declined showed greater increase in severity (1.1 vs .07, p<.001) from baseline to follow-up than pts whose QOL was unchanged, demonstrating sensitivity to change. Conclusions: Breast cancer pts have significant sx burden despite well-preserved PS. The MDASI is a valid, reliable, and sensitive sx assessment method for research and patient care in breast cancer outpatients.
Comparing three validated methods of patient self-reported fatigue in a prospective randomized clinical trial.
Authors: Sams Katherine , Case L. Doug , Lesser Glenn Jay , Naughton Michelle Joy , Williford Susan Kidwell , Giguere Jeffrey Kent , Garino Astrid , Vitolins Mara , Shaw Edward G.
Published: March 2020

9108

Background: Fatigue can be measured with different validated assessment instruments in symptom management trials. Methods: Between 2004-2009, the Wake Forest CCOP Research Base protocol 97202 randomized 236 women receiving adjuvant chemotherapy for newly diagnosed breast cancer to Coenzyme Q10 supplementation vs placebo. The primary endpoint was change in self-reported fatigue. Patients (pt) were assessed at baseline, 8, 16, and 24 weeks (wk) with 3 instruments: 1) Profile of Mood States – Fatigue (POMS; 7 questions; scored 0-4); 2) Functional Assessment of Cancer Treatment – Fatigue (FACIT; 13 questions; scored 0-4); and 3) Visual Analog Scale (VAS; one scale; scored 0-10). For comparison, each instrument was rescaled from 0 to 100; higher numbers indicate worse fatigue. Results: CoQ10 did not significantly affect fatigue (Lesser G et al, ASCO Proc., 2010). All 3 measures demonstrated an increase in fatigue after chemotherapy initiation at 8 & 16 wks with trend towards baseline levels at 24 wks. The fatigue measures were highly correlated: r ≥ 0.8 for all pairwise associations at all times. However, their scores varied. The Table shows mean rescaled scores for pt below/above the median fatigue level, calculated by taking mean of the three scores averaged across the four time periods. In general, POMS tended to give the lowest and VAS the highest scores, but differences between POMS and FACIT and FACIT and VAS depended on mean fatigue level. For pt experiencing lower (median) fatigue, POMS and FACIT scores were similar, while VAS was significantly higher. Conclusions: While POMS, FACIT, and VAS scores were highly correlated, their scale scores varied depending on the level of fatigue experienced by the pt. Fatigue assessment methods in clinical trials should be selected carefully as they do not always give equivalent results. Supported by NCI/DCP grant U10 CA81851. [Table: see text]