bluuebunny/crossref_metadata_2025 huggingface dataset:
Validity and reliability of the patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE).
Authors: Dueck Amylou C. , Mendoza Tito R. , Mitchell Sandra A. , Reeve Bryce B. , Castro Kathleen M. , Denicoff Andrea , O'Mara Ann M. , Rogak Lauren J. , Clauser Steven B. , Bryant Donna M. , Gillis Theresa A. , Bearden James D. , Siegel Robert D. , Harness Jay K. , Paul Diane B. , Cleeland Charles S. , Sloan Jeff A. , Schrag Deborah , Minasian Lori M. , Basch Ethan M.
Published: March 2020

9047

Background: Symptomatic adverse events (AE) in cancer trials are reported by clinicians using the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE). To integrate the patient perspective into AE reporting, NCI contracted (HHSN261201000043C) to create a patient-reported outcomes companion tool (PRO-CTCAE). We report the validity and reliability of PRO-CTCAE’s 124 items reflecting 78 symptomatic AEs. Methods: English-speaking subjects (n=869; 44% male; median [mdn] age 59; 32% racial/ethnic minority; 34% high school or less; 17% ECOG Performance Status [PS] 2-4) receiving treatment for a range of cancers at 4 NCI-designated cancer centers and 5 sites in NCI's Community Cancer Centers Program completed a web-based survey in clinic including PRO-CTCAE and EORTC QLQ-C30. Pearson correlations were computed between PRO-CTCAE items and QLQ-C30 scales. Differences in PRO-CTCAE item scores between clinician-reported ECOG PS (0-1 vs 2-4) groups were computed. Test-retest reliability of 48 prespecified items was evaluated in a subset (n=79). Results: Correlations in the expected direction were observed for 116/124 PRO-CTCAE items with the QLQ-C30 global health scale (mdn r=-.21; range .08 to -.57). Stronger correlations were seen for PRO-CTCAE items with conceptually related QLQ-C30 domains: fatigue with physical, role and social functioning (-.54 to -.66); anxiety and depression with emotional functioning (-.54 to -.70); and concentration and memory problems with cognitive functioning (-.62 to -.72) [all p <0.001]. Fatigue, nausea, vomiting, pain, dyspnea, insomnia, appetite loss, constipation and diarrhea items strongly correlated with corresponding QLQ-C30 symptom scales (.69 to .79, all p <0.001). Scores for 98/124 PRO-CTCAE items were higher in the ECOG PS 2-4 vs 0-1 group (mdn effect size .3). Test-retest reliability was observed across all tested items (mdn intraclass correlation coeff .77; range .53 to .96). Conclusions: Results demonstrate favorable validity and reliability of PRO-CTCAE in a large, heterogeneous sample of patients undergoing cancer treatment. Further testing in multicenter treatment trials is underway.
Smoking habits of relatives of patients (pts) with cancer.
Authors: Hayran Mutlu , Kilickap Saadettin , Elkiran Tamer , Akbulut Hakan , Abali Huseyin , Yuce Deniz , Kilic Diclehan , Turhal Serdar
Published: March 2020

9050

Background: We aimed to determine the rate and habitual patterns of smoking, intentions of cessation, dependence levels and sociodemographic characteristics of relatives of cancer patients. Methods: The smoking habits of relatives of cancer pts were evaluated with a questionnaire and Fagerstrom test (FT) of nicotine dependence. FT and a questionnaire form were filled in by the volunteers. The quit rate of the relatives of the cancer pts was compared with the rates declared in the literature. Results: A total of 560 subjects who have relatives of pts with cancer. The median age of those with lower and higher Fagerstrom scores (FS) were 40 years and 42 years, respectively (p<0.001). We found no association between FS and sociodemographic variables, such as the subject's medical status, gender, living in the same house, educational status, family income, closeness and time spent with the cancer pts. Only 2% of the subjects started smoking after cancer was diagnosed in their relative and almost 20% of subjects had quit smoking within the year. Spontaneous quit rates of these subgroup of smokers (20%) was significantly higher than reported self-quit rates (max. ~10%) in the literature (p<0.001). Conclusions: The FS is known to be helpful in determining who would benefit from a cigarette smoking cessation program. We also show here that the cancer diagnosis in a smoker's family motivates this individual to quit smoking and may create a time window for any involved health staff to intervene for help. This study was designed by the Turkish Oncology Group, Epidemiology and Prevention Subgroup. [Table: see text]
3D index calculated from duration and severity of neutropenia and a degree of fever as prognostic factors predicting mortality of chemotherapy-induced febrile neutropenia in hematologic malignancies.
Authors: Shirasaki Ryosuke , Akiyama Nobu , Tashiro Haruko , Matsuo Takuji , Yamamoto Tadashi , Oka Yoko , Kawasugi Kazuo , Shirafuji Naoki
Published: March 2020

9053

Background: Risk stratification of patients with febrile neutropenia (FN) is important to select the suitable therapeutic option. Although the MASCC scoring system is used as a reliable risk-discriminator, the objective evaluation of “burden of illness” has been difficult to be pointed-out. The latest IDSA Guidelines on FN proposes a set of risk factors based on the expert’s recommendations. The present study demonstrates usefulness of newly proposed 3D-index on predicting mortality of chemotherapy-induced FN in hematologic malignancies (HM). Methods: Patients with HM admitted to our hospital between Jan 2008 and Dec 2011 were enrolled, and data from 282 FN episodes in 129 FN patients including 20 infection-associated deaths were retrospectively analyzed to determine useful prognostic factors on the mortality of FN. Correlation between mortality and 59 characteristics including 3D-index were examined by univariate analysis and receiver operating characteristic curve analysis. 3D-index is a duration and severity of neutropenia and degree of fever. Total duration of days during neutropenia was not calculate at the time of risk evaluation. 3D-indexes after three and five days from the start of FN were also analyzed. Results: 32 out of 59 characteristics were significantly correlated with mortality by univariate analysis. Among them, 3D-index and 3D-indexes after three and five days were demonstrated as more useful factors (3D-index, p=0.0015; 3D-index after three days, p=0.0030; 3D-index after five days, p=0.0044). And 3D-index after three days over 4000 indicates patients' mortality above 20%, index 2600-4000 15-20% , index 900-2600 10-15%, and index below 900 below 10%, respectively. Conclusions: 3D-indexes after three days were suggested as useful predictors for infection-related mortality during FN. It was suggested that FN patients were categorized into four risk groups according to the value.
Comparison of three different radiation fractionation schedules in the palliation of painful bone metastasis.
Authors: Malik Monica , Jilla Swapna , Sesikeran Nanditha , Naidu K. V. Jagannath Rao , Pamidighantam Suresh , Sunkavalli Venkata Ratnam
Published: March 2020

9055

Background: The purpose of this study was to compare the efficacy of a single fraction versus two multifractionated regimens in the palliation of painful bone metastases. Methods: Patients with painful bone metastases were randomized into three groups. Group I received a dose of 8 Gy in a single fraction, Group II received 20 Gy in five fractions and Group III patients received 30 Gy in 10 fractions. Pain score, ECOG performance status and analgesic requirement were recorded at baseline and at 1, 4, 8 and 12 weeks following treatment. Pain score was recorded on a 5-point verbal rating scale from 0 (no pain) to 4 (extremely severe pain). Overall response was defined as decrease in pain score by at least one point. Complete response was defined as achieving a pain score of zero at any point during follow-up. Duration of overall response was defined as the time from initial response till return of pain to its baseline value. Results: 45 patients were included with 15 in each group. Median age was 55 years (range 29-78 years). 17(37.7%) had metastasis in pelvic bones; 17(37.7%) in the spine while the remainder in the appendicular bones. Overall response rates in Groups I, II and III at week 1 were 60%, 53.3% and 60% respectively (p=0.71). At 1 month, overall response rates were 71.4%, 73.3% and 73.3% (p=0.84) and at 3 months; 78.5%, 80% and 80% respectively (p=0.86). The rate of complete response in all the three groups was 20%. Improvement in performance status in Groups I, II and III was seen in 60%, 66% and 80% respectively (p=0.69). Analgesic usage decreased in 86%, 87% and 80% patients in groups I, II and III respectively (p=0.66). Out of the nine complete responders, two sustained the response for less than four weeks, four patients up to eight weeks and remaining three till the end of follow-up. There was no statistically significant difference in between the three arms among all the variables compared. Conclusions: All three groups showed equal efficacy in pain palliation, analgesic requirement, improvement in performance status and duration of response. In patients with very advanced disease and short life expectancy, where the treatment goal is to decrease pain, 8 Gy in single fraction is a convenient and cost effective schedule.
Genetic polymorphisms of SCNA9 as predictive markers of oxaliplatin-induced neuropathy.
Authors: Sereno Maria , Gutierrez-Gutierrez Gerardo , Rodriguez-Antona Cristina , Sanchez Lara , gomez Lopez Cesar , Lopez Gomez Miriam , Zambrana Tevar Francisco , Merino Maria , Miralles Ambrosio , Casado Enrique
Published: March 2020

9073

Background: Oxaliplatin (OXL) is an active drug in digestive tumors. Oxaliplatin induced peripheral neuropathy (OIN) is the main dose limiting toxicity. Around 60-80% of patients developed a mild cold-induced neurotoxicity that used to disappear few days after but in 15% became a persistent neuropathy. The pathophysiology of oxaliplatin-induced neuropathy (OIN) remains unclear, preclinical studies suggest involvement of voltage Na channels. SCN9A gene codifies to Na channels α subunit highly expressed in nociceptive neurons. Mutations in SCN9A are involved in alterations in neuropatic pain perception. This study tried to identify if variants in SCN9A could be associated to a higher risk to OIN. Methods: Serum were obtained from 100 patients with digestive cancer (colorectal, gastric, pancreatic and bile duct) treated with OXL (adjuvant or advanced setting) in Infanta Sofía University Hospital. No diabetes or hypotiroidism were detected. Patients were divided in two groups according to the development of OIN: Arm A 50 patients diagnosed of grade 2-3 OIN after 6 courses and Arm B 50 with no OIN. The evaluation of severity of the OIN by a neurologist included a classification according to NCI-CTC and OSNS scales and conduction studies. Genomic DNA was isolated from serum and variants of SCN9A were analyzed by PCR-RFLP. The relation between SCN9A genotype and the development of severe OIN was the primary aim Results: One hundred patients were enrolled between May 2010-November 2011. 56 (56%) females and 44 (44%) males; mean age was 62; mean ECOG was 1; primary tumor were colorectal 81 pts (81%), gastric 10 (10%); 8 (8%) pancreto-biliar and anus 1(1%). Stage were classified in localized 65 (65%) and advanced (35%). The chemotherapy regimen included: 94 (94%) XELOX, 1 (1%) XELOX-Herceptin and 5 (5%) EOX regimen. The mean of cycles were 7 (1-14). Mean OXL dose intensity was 100mg/m2.The mean PFS was 23 months. High expression of SCN9A variants were detected in patients 26/50, 52% arm A and in 5/50, 10% arm B patients, suggesting a possible relationship beetwen the development of OIN and SCN9A genotype (p=0.04). Conclusions: SCN9A polimorphysms may help to identify those patients with a higher risk to develop oxaliplatin induced neuropathy.
Pilot study of Scrambler therapy for the treatment of chemotherapy-induced peripheral neuropathy.
Authors: Pachman Deirdre R. , Linquist Breanna M. , Barton Debra L. , Fee-Schroeder Kelliann C. , Smith Thomas J. , Lachance Daniel Honore , Liu Heshan , Seisler Drew K. , Loprinzi Charles L.
Published: March 2020

9075

Background: Chemotherapy-induced peripheral neuropathy (CIPN), a common dose-limiting side effect of chemotherapy, remains without known effective interventions. Preliminary data support that Scrambler therapy, a device which treats pain via non-invasive cutaneous electrostimulation, is beneficial for the treatment of CIPN. This pilot trial was performed to investigate the effect of Scrambler therapy for the treatment of CIPN. Methods: Eligible patients included those age ≥18 years, ECOG PS ≤2, life expectancy ≥3 months, with pain or CIPN symptoms of ≥1 month duration and tingling or pain ≥4/10 during the prior week. Patients were treated with Scrambler therapy to the affected area for up to 10 daily 30 minute sessions. Symptoms were monitored daily during therapy using a questionnaire to measure symptoms of neuropathy with a numerical analogue scale. Results: We report on the first 11 CIPN patients, enrolled between 7/18/2011 and 12/12/2011, 3 men and 8 women; mean age 57 years. Patients had history of exposure to various chemotherapeutic agents and the majority had symptoms >2 years. The table portrays data at baseline, at the end of the 10 planned days of therapy, and the percent changes from baseline to the end of treatment, regarding patient reported pain, tingling, and numbness over the preceding 24 hours. There were no adverse events. Persistent benefit out to 5 weeks was seen in some patients; maturing data will be available by May 2012. Descriptive summary statistics formed the basis of data analysis. Further patients are being entered on this trial. Conclusions: Scrambler therapy appears to be beneficial in the treatment of CIPN. A prospective placebo-controlled clinical trial should be performed to confirm these preliminary findings. [Table: see text]
Paucity of core palliative care elements available to children with cancer at end-of-life: Perspectives of bereaved parents and clinicians.
Authors: Kassam Alisha , Habib Sharifa , Skiadaresis Julia , Alexander Sarah , Wolfe Joanne
Published: March 2020

9076

Background: Recognition of serious deficits in palliative care for children has prompted hospitals to develop specialized pediatric palliative care programs. However, only a minority of children who die from advanced cancer receive services from these dedicated programs. We aimed to determine which elements of palliative care are considered important according to bereaved parents and pediatric oncology clinicians and to determine availability of these elements. Methods: We administered questionnaires to 75 bereaved parents (response rate 53%) and 48 pediatric oncology clinicians (response rate 91%) at the Hospital for Sick Children in Toronto, Canada. The main outcome measures were importance ratings and availability of core elements of palliative care delivery based on the National Quality Forum clinical practice guidelines for quality palliative care. Results: Fifteen of the twenty-one core elements were highly valued by both parents and clinicians (defined as > 60% of parents and clinicians reporting the item as important). When compared to clinicians, parents gave higher importance ratings to receiving cancer-directed therapy during the last month of life (p = 0.007) and involvement of a religious or spiritual mentor (p = 0.03). Clinicians gave higher importance ratings to involvement of a social worker (p < 0.0001). Notably, of the valued elements, only three of them were available greater than 60% of the time according to clinicians and parents. Valued elements least likely to be available included a direct admission policy to hospital, involvement of a religious or spiritual mentor, sibling support and parent preparation for medical aspects surrounding death. Conclusions: Children with advanced cancer are not receiving key elements of palliative care despite both parents and clinicians recognizing them as important. Evaluation of barriers to provision of quality palliative care and strategies for overcoming them is critical.
Randomized trial of a physical activity intervention in patients with metastatic breast cancer.
Authors: Ligibel Jennifer A. , Giobbie-Hurder Anita , Shockro Laura , Campbell Nancy , Partridge Ann H. , Tolaney Sara M. , Lin Nancy U. , Winer Eric P.
Published: March 2020

9084

Background: Physical activity (PA) interventions improve fitness, functional capacity, and quality of life in patients with early-stage breast cancer. There are almost no data regarding the feasibility or potential benefits of PA in women with metastatic breast cancer (MBC). Our study evaluated the impact of a moderate-intensity PA intervention upon functional measures in patients with MBC. Methods: Participants were randomized 1:1 to a 16-week PA intervention or usual care control group. Eligibility included diagnosis of MBC, ECOG 0-1, and no active brain metastases. The intervention consisted of 4 weekly meetings with an exercise physiologist, followed by monthly in-person and weekly telephone-based meetings. The PA goal was 150 minutes per week. Baseline and 16-week evaluation included: modified Bruce treadmill test, 7-Day Physical Activity Recall Interview, and EORTC QLQ C-30 questionnaire. Results: 101 women enrolled between 9/06 and 3/11. Median age was 49 years, median time since diagnosis of MBC was 1.1 years, 48% of participants were on hormonal therapy and 42% on chemotherapy/biologic therapy. 69% completed all study measures (an additional 9% all but the final treadmill test). Attrition was higher in the intervention arm (30% vs. 16%, p=0.15). Outcome measures are shown in table below. Both groups experienced improvements in treadmill times. Intervention participants also reported improvements in physical functioning and increased minutes of weekly PA, with a trend toward significant differences between groups. Conclusions: Women with MBC participating in a PA intervention experienced consistent, but non-significant, trends toward improvements in functional measures. Our sample size was small, limiting power to evaluate the potential benefits of PA in women with MBC. Additional work is warranted, particularly since PA interventions appear feasible in this patient population. [Table: see text]
Usefulness of medical oncologists’ estimates of survival time in people with advanced cancer.
Authors: Kiely Belinda E. , Martin Andrew J. , Tattersall Martin HN , Nowak Anna K. , Goldstein David , Wilcken Nicholas , Wyld David , Beale Philip James , Jefford Michael , Glasgow Amanda L. , Abdi Ehtesham A. , Glare Paul A. , Stockler Martin R.
Published: March 2020

9087

Background: We sought to determine the calibration, precision, prognostic significance and suitability of estimated survival time (EST) as a basis for estimating and explaining prognosis in advanced cancer. Methods: Medical oncologists recorded their EST as the “median survival of a group of identical patients” in patients with advanced cancer and a life expectancy >3 months recruited to a randomized trial of sertraline (Lancet Oncol 2007; 8: 603). Calibration, precision and suitability were defined by the proportions of patients whose observed survival times (OST) were bounded by simple multiples of their EST (based on our previous studies), i.e. 50% expected to live longer (or shorter) than their EST; 30% expected to live from 0.75 to 1.33 times their EST (arbitrary criterion for precision); 50% expected to live from half to double their EST (range for typical scenario); 10% expected to live >3 times their EST (best case scenario), or <¼ of their EST (worst case scenario). Results: Characteristics of the 114 patients were: median age 63 years, Karnofsky performance status (KPS) ≤70 in 25%, and a median of 8.5 months since diagnosis of advanced cancer. Primary cancer sites included breast (18%), colorectal (16%), lung (15%), prostate (12%) and ovary (10%). Median survival was 10.6 months after a median follow-up of 14 months and 68 deaths. EST were well-calibrated: 54% of patients lived longer than their EST and 46% lived shorter than their EST. EST were imprecise (21% within 0.75 to 1.33 times OST) but equally likely to be over-optimistic (34% >1.33 x OST) or over-pessimistic (39% <0.75 x OST). 6% of patients lived <¼ of their EST; 62% lived from half to double their EST and 9% lived >3 times their EST. Independently significant predictors of OST in a multivariable Cox model included EST (HR=0.92, p=0.004), dry mouth (HR=5.07, p<0.0001), alkaline phosphatase >101U/L (HR=2.80, p=0.0002), KPS ≤70 (HR=2.30, p=0.007), prostate primary (HR=0.23, p=0.002), and steroid use (HR=2.35, p=0.02). Conclusions: Medicaloncologists’ EST were well-calibrated, imprecise, independently associated with OST, and useful for estimating and explaining best case, worse case, and typical scenarios for survival time in patients with advanced cancer.
Incidence, characteristics, and associations of oxaliplatin-induced peripheral neuropathy in colorectal cancer patients: Results of a prospective, multicenter, international study.
Authors: Argyriou Andreas , Alberti Paola , Briani Chiara , Velasco Roser , Bruna Jordi , Campagnolo Marta , Cazzaniga Marina Elena , Bergamo Francesca , Cortinovis Diego Luigi , Santos Cristina , Papadimitriou Konstantinos , Cavaletti Guido , Kalofonos Haralabos
Published: March 2020

9090

Background: We sought to trace the incidence and severity of oxaliplatin-induced peripheral neuropathy (OXLIPN) and to determine its clinical pattern. Among other associations, we also specifically aimed at testing whether the degree of acute neuropathy is clinically related to the development and severity of chronic OXLIPN. Methods: 170 patients (mean age 64y), scheduled to be treated with either FOLFOX or XELOX for metastatic colorectal cancer were studied. Patients were prospectively monitored at baseline and followed-up during chemotherapy in four European sites. The motor/neurosensory NCI-CTCv3 criteria and the clinical version of the Total Neuropathy Score were applied to clinically grade the severity of OXLIPN. Nerve conduction studies were also longitudinally performed. Results: Evidence of acute OXLIPN was disclosed in 146/170 patients (85.9%). The vast majority of patients manifested cold-induced perioral (95.2%) or pharyngolaryngeal dysesthesias (91.8%). Other uncommon symptoms, such as jaw spasm were also present. Severe acute OXLIPN, requiring prolongation of OXL infusion from 2 to 4-6 hours was evident in 32/146 patients (21.9%). Overall, 123/170 patients (72.4%) experienced chronic OXLIPN. Severities were grade I: 39 (22.9%); grade II: 52 (30.6%); grade III: 33 patients (19.4%). Worst severities were related to cumulative oxaliplatin dose (r:0.269;p<0.001). Follow-up assessments revealed significant decrease in all sensory action potentials examined. The severity of the acute OXLIPN was significantly correlated with both the development (r:0.450;p<0.001) and degree of the chronic form (r:0.703;p<0.001). Conclusions: Most patients treated with oxaliplatin-based chemotherapy would manifest OXLIPN, mainly of moderate degree. The severity of the acute syndrome appears to clinically correlate with the degree of the chronic form of OXLIPN. Our data suggest that acute phenomena, related to axonal hyperexcitability, could contribute to the development of peripheral neuropathy; thus it could be advisable to test agents against acute OXLIPN in order to verify their effects on the chronic form.
Sexual functioning in young women with breast cancer.
Authors: Rosenberg Shoshana , Tamimi Rulla M. , Gelber Shari I. , Ruddy Kathryn Jean , Kereakoglow Sandra , Borges Virginia F. , Come Steven E. , Schapira Lidia , Winer Eric , Partridge Ann H.
Published: March 2020

9100

Background: Sexual dysfunction is a known complication of adjuvant therapy for breast cancer and an important determinant of quality of life. Little is known about the frequency and magnitude of this problem among very young women with breast cancer during the year following diagnosis. Methods: 298 sexually-active women enrolled in an ongoing multi-center cohort study with Stage 0-III breast cancer at or before age 40 were included in this analysis. Treatment data was self-reported on a survey mailed to participants at enrollment. Sexual functioning was assessed using the sexual interest and dysfunction subscales from the Cancer Rehabilitation Evaluation System (CARES). Scores range from 0-4, with higher scores indicative of poorer function. The survey included a measure of anxiety and depression (Hospital Anxiety and Depression Scale), of body image (CARES) and of physical and menopausal symptoms (Breast Cancer Prevention Trial Symptom Checklist). Mean differences in CARES scores between treatment groups (chemotherapy vs. none; hormone therapy vs. none; lumpectomy vs. mastectomy vs. mastectomy + reconstruction vs. no surgery; radiation vs. none) were compared using T-tests and ANOVA. Multiple regression models were fit to assess symptoms thought to be mediators of the treatment-sexual functioning association. Results: Mean age at diagnosis was 36 (range: 22-40) years and mean time from diagnosis to survey completion was 5 months (range: 1-16). Mean CARES sexual interest and dysfunction scores were higher in women who received chemotherapy compared to those who did not (p<0.0001). In the multivariate analysis, chemotherapy was no longer associated with decreased sexual interest or function. Anxiety, depression, musculoskeletal pain, and poorer body image were predictive of both decreased sexual interest and function. Vaginal pain symptoms were associated with greater dysfunction, while unhappiness with appearance was associated with decreased interest. Conclusions: Young women who receive chemotherapy are at risk for problems related to sexual functioning early in the survivorship period. This effect appears to be mediated through several physiologic and psychologic mechanisms, underscoring the need for interventions that target both.
Anemia and functional disability in older adults with cancer.
Authors: Owusu Cynthia , Tew William P. , Hardt Molly , Mohile Supriya Gupta , Klepin Heidi D. , Gross Cary P. , Gajra Ajeet , Lichtman Stuart M. , Ramani Rupal , Katheria Vani , Zavala Laura , Hurria Arti
Published: March 2020

9109

Background: While anemia is associated with functional disability in older adults in general, this relationship has not been well characterized in older adults with cancer. We sought to examine the association between anemia and functional disability and to identify other factors associated with functional disability in patients (pts) age ≥65 with cancer. Methods: We conducted a secondary analysis of a multi-center prospective study of 500 pts ≥ age 65 that identified predictors of chemotherapy (chemo) toxicity (Hurria et al, JCO, 2011). The primary outcome of this analysis was functional disability, defined as need for assistance with ≥1 instrumental activities of daily living. Data collected prior to initiation of a new chemo regimen included: age, tumor/treatment variables, labs [including hemoglobin (Hb)], and geriatric assessment (functional status, comorbidity, social support, psychological, cognitive, and nutritional status). Anemia (World Health Organization criteria) was defined as Hb <12g/dl (women) and Hb <13g/dl (men). Bivariate analysis and logistic regression were used to examine the association between functional disability, anemia, and other pre-treatment variables. Results: Among 500 pts [median age 72 years (range 65-91), 56% female, 61% stage IV], the prevalence of functional disability and anemia was 43% and 51%, respectively. The mean Hb was 11.7g/dl and 12.6g/dl among pts with and without functional disability. Pts with anemia were more likely to report functional disability (53% vs. 46%, p<0.01). On multivariate analysis, factors associated with functional disability included anemia [Odds Ratio (OR)= 2.06, 95% confidence interval (CI)= 1.39-3.05], increased age (OR= 1.04, 95% CI = 1.00-1.07), increased comorbidity (OR= 1.23, 95% CI = 1.09-1.39), advanced stage (OR= 1.85, 95% CI = 1.22-2.80), and unintentional weight loss (OR= 2.02, 95% CI = 1.37-3.00). Conclusions: Anemia was highly prevalent and was associated with functional disability. Prospective studies that further examine the relationship between anemia and functional disability and randomized-controlled trials that evaluate the correction of anemia as a modifiable strategy to improve functional status in older pts with cancer are warranted.
Pain, sleep disturbance, and fatigue symptom cluster in patients suffering from chronic chemotherapy-induced neuropathic pain (CINP).
Authors: Gewandter Jennifer S. , Heckler Charles E , Devine Katie , Mohile Supriya Gupta , Palesh Oxana , Roscoe Joseph , Morrow Gary R. , Bury Martin Joseph , Jacobs Andrew
Published: March 2020

9113

Background: Various symptom cluster combinations of pain, fatigue, sleep disturbance (SD), and depression have been identified in cancer patients. The presence of symptom clusters has not been assessed in patients with persistent CINP. This exploratory analysis aimed to determine which symptoms statistically clustered with pain in cancer survivors with CINP. Methods: The University of Rochester Cancer Center Community Clinical Oncology Program recruited 461 patients with CINP > 4 (on a 0-10 scale) who had completed chemotherapy (median 7 months ago) for a pain intervention trial. At baseline, groups of highly associated symptoms that included pain were identified empirically using factor and cluster analyses of the 11 symptoms in the University of Rochester Symptom Inventory plus the Hospital Anxiety and Depression Scale (HADS) scores. To investigate if associated symptoms track together over time, multiple linear regression (MLR) analysis was performed using changes in symptom severity between baseline and week 6, controlling for gender, age, education, race, and marital status. Results: Subjects were 88% white and 71% female, and on average 61 years old. Mean (standard deviation) baseline pain, fatigue, and SD were 5.7 (2.8), 5.0 (2.7), and 4.2 (3.1), respectively; 26% of subjects had borderline or abnormal HADS scores. Factor analysis identified 3 factors that accounted for 88% of the variance. One factor included pain, fatigue, SD, but not HADS, and accounted for 37% of the variance. Variable clustering also identified pain, SD, and fatigue as 1 symptom cluster. Changes in severity of SD and fatigue (p < 0.0001), but not HADS, were associated with changes in pain (adjusted R2 = 0.168) in MLR analysis. Conclusions: Pain, fatigue, and SD were identified as a symptom cluster by factor and cluster analyses, and were found to track together over time by MLR. Since these data suggest that pain is associated with sleep quality and fatigue in patients with persistent CINP, targeting one of these symptoms may lead to reductions in the others. Future research should investigate interventions that target pain, fatigue, and SD concurrently in cancer survivors suffering from CINP.
Evaluation of a non-peptidic mimic of host defense proteins, PMX30063, in an animal model of oral mucositis.
Authors: Scott Richard W , Korczak Bozena , Watkins Brynmor A , Sonis Stephen T.
Published: March 2020

9119

Background: Oral ulcerative mucositis (OM) is a common, painful, dose-limiting toxicity of cancer therapy. The care for OM is largely palliative and there is an urgent need for new and effective therapies. Host defense proteins (HDPs) are amphiphilic components of the innate immune system that serve as a primary response to infection. Exclusive of their direct antimicrobial activity, HDPs have been shown to possess immune modulatory and anti-inflammatory activities. We are developing non-peptidic mimics of HDPs, capturing the structural and biological properties of HDPs within a framework of smaller fully synthetic oligomers. The lead compound, PMX30063, is in Phase 2 clinical trials for iv treatment of systemic staphylococcal infections. Recently, we observed that HDP mimics attenuate anti-inflammatory pathways and reasoned that these activities could be leveraged into a mucositis intervention. Methods: In an acute radiation hamster model, PMX30063 was applied as a topical rinse, 3 times daily at 1, 3 or 10 mg/ml over a 28 day treatment regimen ( n = 10), following a single radiation dose to the buccal cheek pouch (40 Gy). In a fractionated radiation model, radiation (7.5 Gy/dose) was administered on days 0, 1, 2, 3, 6, 7, 8 and 9, targeting the left buccal pouch mucosa. PMX30063 was given topically 3 times daily at 3 mg/ml over a 35 day regimen beginning on day 0 (n = 10). OM was scored using an established blinded method. Results: In the acute model, PMX30063 reduced the number of animal days with ulceration from 43% in vehicle-treated hamsters to < 5% in all 3 PMX30063 dose groups (χ2 test; p<0.001). In the fractionated model, PMX30063 significantly reduced the daily mucositis scores prior to peak mucositis and throughout the remaining course of treatment (Mann-Whitney Rank-sum analysis; p<0.001). PMX30063 reduced the number of animal days with ulceration from 55% in vehicle-treated hamsters to 3.3% (χ2 test; p<0.001). The time courses of efficacy argue that direct antimicrobial action is not the primary driver of efficacy. Conclusions: The safe and highly efficacious activity of PMX30063 in animals supports its further development as a topical therapeutic to prevent OM in cancer patients.
Efficacy and safety of balugrastim compared with pegfilgrastim in patients with breast cancer who are receiving chemotherapy.
Authors: Volovat Constantin D. , Gladkov Oleg , Bondarenko Igor , Barash Steven , Buchner Anton , Avisar Noa , Bias Peter
Published: March 2020

9125

Background: Patients receiving cancer chemotherapy are at an increased risk of neutropenia. Recombinant granulocyte colony stimulating factors (G-CSFs) have been developed to stimulate proliferation and differentiation of neutrophils. Pegfilgrastim is a pegylated recombinant G-CSF that allows for once-per-cycle dosing. Balugrastim is a long-acting G-CSF composed of a genetic fusion between recombinant human serum albumin and G-CSF. The objective of this study was to compare the efficacy and safety of balugrastim and pegfilgrastim in patients with histologically or cytologically confirmed breast cancer who were scheduled to receive doxorubicin and docetaxel. Methods: In this double-blind, randomized, active-comparator, noninferiority trial, patients with ≥1.5x109 neutrophils/L, and ≥100x109 platelets/L were randomly assigned to subcutaneous injections of balugrastim 40 mg (n=153) or pegfilgrastim 6 mg (n=151) with stratifications for weight, prior chemotherapy exposure, and global location. The primary efficacy endpoint was the duration of severe neutropenia (days with an absolute neutrophil count <0.5x109 cells/L) during the cycle 1 for the population of patients who did not have major protocol violations. Results: Mean duration of severe neutropenia in cycle 1 was 1.1 days in the balugrastim group and 1.0 days in the pegfilgrastim group (95% CI for difference between groups -0.13 to 0.37). Fifty-eight percent of patients in the balugrastim group and 59% in the pegfilgrastim group had severe neutropenia during cycle 1 (95% CI for difference between groups -11.98% to 10.41%). Two and 4 patients, respectively, had febrile neutropenia during cycle 1; no patients in either group had febrile neutropenia during cycles 2-4. Twenty percent of patients in the balugrastim group and 19% in the pegfilgrastim group had adverse events that the investigator considered to be related to study medication. Six and 7 patients, respectively, had serious adverse events. Conclusions: The results of this study support the noninferiority of balugrastim versus pegfilgrastim, demonstrating that both compounds have comparable efficacy. There were no unexpected safety events.
A prospective study of family conferences (FCs) in a palliative care unit (PCU) at a comprehensive cancer center.
Authors: Dev Rony , Coulson Luke C , Pulivarthi Kalyan , Del Fabbro Egidio , Palla Shana L. , Yennurajalingam Sriram , Bruera Eduardo
Published: March 2020

9127

Background: TheFC provides the family information and emotional support in the transition to end-of-life care. There are a few, mainly qualitative, studies of FCs in a palliative care setting. A retrospective report suggested increased emotional expression by family members when patients were not present in the FC. The purpose of our study was to determine the characteristics of FCs and the effect of patient participation on emotional expression by family members. Methods: A prospective study was conducted during 18-month period with140 consecutive FCs conducted by an interdisciplinary team (palliative care physician, social worker, and others). Data collected included demographics, discharge disposition, number of participants, caregiver characteristics, expressions of emotional distress, conflict with healthcare providers, and topics discussed. Descriptive statistics and frequencies were calculated. Analysis was performed using a chi-square test. Results: 70 patients (50%) were female, 64 (46%) white, 127 (91%) with solid tumors and a median age of 59. In 68/140 family meetings (49%), patients actively participated. The primary caregivers were predominantly female (66%), white (49%), and either the spouse or partner (59%). A median number of 4 family members and 4 healthcare providers attended the FCs with median duration of 1 hour and median of 2 days prior to discharge. Questions concerning advanced directives, symptoms anticipated at death and caregiver well-being were infrequent. Patients verbalized distress frequently, (73.1%). Primary caregivers emotional expression of verbal distress were high but not significantly affected by patient presence (82% vs 82%, P:NS); however, verbal expressions of emotional distress by family were more common when patients were absent (87%) than when present (73%), p = 0.037. Conclusions: There was a high frequency of expression of emotional distress by patients and family members. Patient participation was associated with decreased verbal emotional expression by family members but not the primary caregiver. Further studies are needed on the benefits of allocating additional time to meet with family members without patient presence during a FC.
Palonosetron (PALO) plus 1-day versus 3-day dexamethasone (DEX) with or without aprepitant against delayed nausea (DN): Pooled analysis for 554 women receiving highly emetogenic chemotherapy (HEC).
Authors: Celio Luigi , Longo Flavia , Mansueto Giovanni , Lapadula Vittoria , Agustoni Francesco , Aapro Matti S.
Published: March 2020

9133

Background: Nausea is more difficult to control than vomiting, because the incidence of the symptom continues to rise over the days after chemotherapy. This post-hoc analysis addressed two questions: 1) Does PALO plus single-dose DEX result in suboptimal control of DN when compared to the same regimen with additional DEX doses? 2) Is the combination of PALO, DEX, and aprepitant a more effective coverage against DN? Methods: The analysis was based upon outcomes in chemo-naïve women (median age =52) with solid tumors (89% breast) enrolled in two Phase III and two Phase II trials of HEC (AC combination or cisplatin). Patients received the following regimens: 1) PALO 0.25 mg plus DEX 8 mg IV on day 1 of chemotherapy (1-day regimen, n=243); 2) the same regimen on the day 1 followed by DEX 8 mg orally on days 2 and 3 (3-day regimen, n=207); or PALO plus DEX plus aprepitant 125 mg on day 1 followed by aprepitant 80 mg on days 2 and 3 (triple regimen, n=104). The pre-specified primary endpoint was the proportion of patients with no DN (days 2-5 after the first cycle of chemotherapy). The two primary comparisons were 1-day vs. 3-day regimen, and triple vs. 3-day regimen, with statistical significance set to the 0.025 level. Results: The 1-day to 3-day regimen comparison was not statistically significant (44% vs. 47.8%; risk difference (RD) = -3.8%, 95% CI (-5.4 to 12.9%), P=0.421 (two-sided chi-square test). The triple to 3-day regimen comparison was also not significant (57.7% vs. 47.8%), RD= +9.9%, 95% CI (-1.9 to 21.3%), P=0.101. More patients receiving triple regimen experienced no acute-onset nausea compared with those administered only DEX (97.1% vs. 51.2%, P<0.0001). Conclusions: This analysis provides evidence that PALO plus 1-day or 3-day DEX yield similar prevention of DN. The addition of aprepitant does not improve the control of DN. Complete results utilizing a multivariable model accounting for risk factors and trial heterogeneity will also be presented.
Outpatient chemotherapy supportive care: Trial of an IT-integrated, NP-delivered system for unrelieved symptoms.
Authors: Mooney Kathi , Beck Susan L. , Wong Bob , Dunson William A. , Wujcik Debra
Published: March 2020

9137

Background: We tested an automated computer based remote monitoring system paired with nurse practitioner (NP) follow up using a case management system to address unrelieved symptoms. Methods: Prospectively 336 patients beginning a course of chemotherapy were randomized to the Telephone Care NP (TC) intervention (n 174) or usual care (UC) (n 162). All called daily reporting presence, severity, and distress (0-10 scale) for 11 common symptoms. Those in the TC intervention also received automated tailored symptom self-care messages and, based on automated alerts for unrelieved symptoms at moderate or higher levels, NP calls to further treat symptoms utilizing national guidelines. Results: There were no differences between groups on any demographics: 84% White, 56 years old, female (77%), breast (45%) or lung (17%) cancer. Average study days were 73 with 87% call completion. Prevalence of participants reporting moderate to severe symptoms were fatigue (86%), pain (80%), sleep (78%), nausea (60%), depressed mood (52%), anxious (49%), trouble thinking (48%), numbness (43%), sore mouth (38%), diarrhea (38%), and appearance concerns (35%). Mixed modeling with intention to treat was used to compare overall symptom scores by treatment condition (TC/UC) while accounting for individuals. Results indicate the TC group mean symptom score was significantly lower than UC (mean difference = .30, p < .001). Also, each symptom was significantly lower for the TC group except for diarrhea. Poisson regression showed TC had lower Severe days than UC (est. means and SE) 3.16 (0.44) vs 10.24 (1.84), p < .001; and lower Moderate days 8.91 (1.04) vs 19.06 (2.22), p < .001. TC had somewhat higher Mild days than UC 19.85 (2.81) vs 13.75 (1.85), p = .06; and more No symptom days 66.06 (3.82) vs 52.02 (4.15), p = .01. Mixed modeling was used to explore TC intervention impact following NP calls for alerts. TC reduced symptom scores compared to UC over a 4 day period (mean difference = 1.28, p< .001). Conclusions: Remote telephone monitoring of symptoms after chemotherapy with nurse practitioner follow up on moderate and severe symptoms results in decreased symptom severity, distress, fewer severe and moderate days and more no symptom days.
Relationship of divergent ancestral genetic variation on chromosome 6p22 and racial disparities in survival in neuroblastoma.
Authors: Pinto Navin R. , Gamazon Eric R , Konkashbaev Anuar , Im Hae Kyung , Diskin Sharon , London Wendy B. , Maris John M. , Dolan M. Eileen , Cox Nancy J , Cohn Susan Lerner
Published: March 2020

9516

Background: An increased prevalence of high-risk disease and worse outcome are observed in children with neuroblastoma who self-report as black versus white. We sought to determine whether genetic variation would explain this racial disparity. Methods: After quality control, we analyzed 511,836 germline genetic variants in 2,709 ethnically diverse children with neuroblastoma enrolled on Children’s Oncology Group study ANBL00B1 from 2001 to 2009. Genetic variation was summarized by conducting principal components analysis. The first principal component (PC1) separated patients with African ancestry from all others. PC1 was used as a continuous variable for ordinal regression with risk group and a Cox proportional hazard model of EFS. To identify genetic mechanisms for the observed disparities, we developed a method using genome-wide variation data applied to high-risk versus non-high risk samples. We identified a comprehensive list of loci with significant divergence between the ancestral populations. We then tested each such locus for association with high-risk phenotype using logistic regression with the proportion of African ancestry estimated by ADMIXTURE as covariate. Finally, top SNPs were added to multivariate models of both risk and event-free survival to determine if any top associations could abrogate observed disparities. Results: PC1 was associated with both risk (p = 0.007) and EFS (p = 0.037). We identified 72 population-divergent SNPs nominally associated with high-risk disease (p < 0.001). The risk allele for one of the top SNPs: rs9295536 (p = 9.2x10-8) was more common in the African ancestral population, was associated with high-risk phenotype and poor outcome in all patients and validated in a Caucasian-only subanalysis. In multivariate testing, this SNP abrogated the PC1 association with EFS (p = 0.18). Conclusions: A SNP with high divergence between ancestral populations on chromosome 6p22 accounts for the observed racial disparity in survival and is also a common genetic variant associated with survival in patients derived from either European or African ancestry (Bonferroni adjusted p < 0.05). Studies to elucidate the function of this SNP are underway.
Phase II study of temozolomide in combination with topotecan (TOTEM) in relapsed or refractory neuroblastoma and other pediatric solid malignancies: A European ITCC study.
Authors: Di Giannatale Angela , Mc Hugh Kieran , Dias Nathalie , Devos Annick , Geoerger Birgit , Jaspan Tim , Calmon Raphael , Courbon Frederic , Malekzadeh Katty , Aerts Isabelle , Verschuur Arnauld , Casanova Michela , Fouyssac Fanny , Rubie Herve , Corradini Nadege , Perel Yves , Zwaan Michel , Riccardi Riccardo , Le Deley Marie-Cécile , Caron Huib
Published: March 2020

9517

Background: Temozolomide and topotecan have shown activity in several pediatric cancers, including neuroblastoma. Resistance to alkylating agents due to MGMT expression, MMR deficiency or microsatellite instability may be overcome through the combination with topoisomerase I inhibitors. The combination of temozolomide and topotecan (TOTEM) was well tolerated and showed preliminary activity in children with neuroblastoma and glioma (Rubie et al, 2010). Methods: This multicenter, non-randomized, multi-cohort Phase II study included children with neuroblastoma according to a 2-stage Simon design, and patients with central nervous system (CNS) and extra-cranial solid tumors in a descriptive design. Temozolomide was administered orally at 150 mg/m2 followed by topotecan at 0.75 mg/m2 intravenously for 5 consecutive days every 28 days. The main endpoint was objective response (OR), i.e., Complete or Partial Response (CR+PR), evaluated after 2 cycles according to WHO criteria, or INRC criteria for neuroblastoma patients with mIBG-positive lesions, by an independent radiological review. Independent review of mIBG imaging is pending. Results: 103 patients, median age 9.4 years (range 1-21), were treated between June 2009 and May 2011 in 18 centers: 38 neuroblastoma, 33 CNS tumors and 32 other solid tumors. Overall 420 cycles were administered (median 3 per patient; range 1-12). Grade 3 or 4 neutropenia was frequent (55% courses), though only 6% of patients developed febrile neutropenia. In the neuroblastoma cohort, 1 CR and 7 PR were observed, leading to an estimated OR rate of 21% (95%CI, 10-37%). Additionally 22 patients had disease stabilization (SD), leading to an overall tumor control (CR+PR+SD) of 79% (63-90%), and a 12-month progression-free survival rate of 47% (31-64%). Overall, 17/102 evaluable patients achieved an OR (17%, 10-25%), with 1 CR and 3 PR in 9 medulloblastoma (44%, 14-79%), 2 PR in 4 PNET, 1 PR in 12 malignant glioma, and 2 PR in 9 RMS. Conclusions: Temozolomide-topotecan combination results in significant tumor control in children with neuroblastoma and medulloblastoma/PNET with favorable toxicity profile.