bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of palmar-plantar erythrodysesthesia and hypothyroidism in patients with metastatic cancer treated with cabozantinib: A systematic review and meta-analysis of randomized controlled trials.
Authors: Thein Kyaw Zin , Zaw Myo , Han Myat M. , Teerakanok Jirapat , Jones Catherine , Tijani Lukman , Hardwicke Fred L. 
Published: November 2017

204 Background: Cabozantinib is an oral inhibitor of multiple tyrosine kinases, including VEGFR, KIT, RET and MET, and is proven to be beneficial in different types of tumors. Nevertheless, there are noteworthy safety concerns. We performed a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of palmar-plantar erythrodysesthesia (PPE) and hypothyroidism among patients with metastatic cancer treated with cabozantinib. Methods: We systematically conducted a comprehensive literature search using MEDLINE, EMBASE databases and meeting abstracts through January 31, 2017. The randomized controlled phase 3 trials that mention PPE and hypothyroidism as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio (RR), and risk difference (RD) with 95% confidence interval (CI). Random effects model was applied. Results: Three phase 3 RCTs with a total of 1999 patients were eligible for analysis. Studies compared cabozantinib (C) vs everolimus, C vs placebo, C vs prednisone, were included in the analysis. All grade-PPE incidence was 499 (36.6%) in cabozantinib arm vs 26 (3.36%) in control arm with a RR of 13.998 (95% CI: 5.409 – 36.224, P < 0.0001). The absolute RD was 0.374 (95% CI: 0.258 – 0.489, P < 0.0001). High-grade PPE was reported in 93 (7.58%) in cabozantinib group vs 3 (0.39%) in control group with a RR of 12.486 (95% CI: 4.529 – 34.426, P < 0.0001). The RD was 0.080 (95% CI: 0.045 – 0.115, P < 0.0001). The overall incidence of hypothyroidism was noted in 292 (23.82%) in cabozantinib arm vs 24 (3.1%) in control arm. The pooled RR of hypothyroidism was 15.825 (95% CI: 1.229 – 203.820, P = 0.034) and RD was 0.237 (95% CI: 0.113 – 0.361, P < 0.0001). Conclusions: Our meta-analysis demonstrated that cabozantinib contributed to significant toxicity of all-grade and high-grade PPE as well as hypothyroidism. Identifying these toxicities may aide physicians in providing good supportive care and patients’ quality of life.
Risk of hematological toxicities and febrile neutropenia in patients with hormone receptor-positive HER2-negative metastatic breast cancer treated with CDK 4/6 inhibitors: A systematic review and meta-analysis of randomized controlled trials.
Authors: Zaw Myo , Thein Kyaw Zin , Tun Aung , Han Myat M. , Radhi Saba , Hardwicke Fred L. , Jones Catherine 
Published: November 2017

207 Background: Majority of breast cancers express the estrogen receptor or progesterone receptor. CDK4/6 signaling plays a role in endocrine therapy resistance and the benefit of inhibition of these pathways has been proven in studies. Yet the impact of these agents on hematological toxicities and febrile neutropenia is a considerable safety concern. Hence, we performed a systematic review and meta-analysis of randomized controlled trials (RCT). Methods: MEDLINE, EMBASE databases and meeting abstracts from inception through June 2017 were queried. RCTs that mention anemia, thrombocytopenia, leukopenia, neutropenia and neutropenic fever as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio with 95% confidence interval (CI). Random effects model was applied. Results: Five RCTs (four phase 3 and one phase 2 studies) with a total of 2671 patients were eligible for analysis. The study arm used palbociclib-letrozole, palbociclib-fulvestrant, ribociclib-letrozole and abemaciclib-fulvestrant while the control arm utilized placebo in combination with letrozole or fulvestrant. The relative risks (RR) of all-grade side effects were as follows: anemia, 3.77 (95% CI: 2.47 – 5.75, p < 0.0001); thrombocytopenia, 9.69 (95% CI: 4.26 – 22.04, p < 0.0001); leukopenia, 11.68 (95% CI: 8.19–16.65; p < 0.0001); and neutropenia, 14.09 (95% CI: 10.73–18.49; p < 0.0001). The RR of high-grade adverse effects were as follows: anemia, 2.66 (95% CI: 1.29 – 5.45, p = 0.008); thrombocytopenia, 7.08 (95% CI: 1.95 – 25.74, p = 0.003); leukopenia, 33.58 (95% CI: 14.49–77.77; p < 0.0001); and neutropenia, 40.33 (95% CI: 19.34–84.10; p < 0.001). The pooled risk of neutropenic fever was statistically significant at 4.26 (95% CI: 1.11–16.26; p = 0.034). Conclusions: CDK 4/6 inhibitors based regimen significantly contributed to all hematological toxicities as well as febrile neutropenia. These toxicities affect patients’ quality of life, add financial burden and may lead to drug dosing inconsistencies.
Outcomes of a specialized interdisciplinary approach for cancer patients with aberrant opioid-related behavior: A preliminary report.
Authors: Edwards Tonya , Arthur Joseph Anthony , Reddy Suresh , Nguyen Kristy , Hui David , Yennu Sriram , Park Minjeong , Liu Diane D , Bruera Eduardo 
Published: November 2017

212 Background: Data on the development and outcomes of effective interventions to address aberrant opioid-related behavior (AB) in cancer patients is lacking. Our outpatient supportive care clinic developed and implemented a specialized interdisciplinary team approach to manage patients with AB. The purpose of this study was to report clinical outcomes of this novel intervention. Methods: The medical records of 30 consecutive patients with evidence of AB who received the intervention and a random control group of 70 patients without evidence of AB between January 1, 2015 and August 31, 2016 were reviewed. Results: At baseline, pain intensity (p=0.002) and opioid dose (p=0.001) were significantly higher among patients with AB. During the course of the study, the median number of ABs per month significantly decreased from 3 pre-intervention to 0.4 post-intervention (p<0.0001). The median morphine equivalent daily dose decreased from 165mg/day at the first intervention visit to 112mg/day at the last follow up (p=0.018) although pain intensity did not significantly change (p= 0.984). ‘Request for opioid medication refills in the clinic earlier than the expected time’ was the AB with the highest frequency prior to the intervention and the greatest improvement during the study period. Younger age (p<0.0001) and higher ESAS anxiety score (p=0.005) were independent predictors of the presence of AB. Conclusions: The intervention was associated with a reduction in the frequency of AB and opioid utilization among cancer patients receiving chronic opioid therapy. More research is needed to further characterize the clinical effectiveness of this intervention. [Table: see text]
A comparison of Numeric Pain Rating Scale (NPRS) and the Visual Analog Scale (VAS) in patients with chronic cancer-associated pain.
Authors: Firdous Shagufta , Mehta Zankhana , Fernandez Carlos , Behm Bertarnd , Davis Mellar 
Published: November 2017

217 Background: Though numerical rating scales (NRS) are frequently used, a subset of patients do not understand the abstract nature on NRS and use quality descriptors of severity. We used a visual analog scale (VAS) using descriptors of “good day”, “average day” and “bad day” along a 10-cm line and compared it to a NRS in patients with cancer diagnosis and pain 1 month or longer. Methods: Eligible patients were verbally consented and completed the two scales. We asked patients thoughts about which they felt was the more appropriate scale to gauge their pain. The scales were compared by the distance from the extreme left of the line to the mark the patient placed on the VAS. Additional data included demographic and diagnosis information. The VAS and NRS were compared using two-sample t-tests or Wilcoxon rank-sum tests and Pearson’s chi-square or Fisher’s exact tests, as appropriate. The relationship between the numeric pain scale and the visual analog scale is described using Pearson’s correlation coefficient. Results: Full data was provided from 94 patient surveys who completed surveys. The mean age was 61 years old, 56.4% were female, and 78.0% had metastatic cancer. Numerous cancer types were reported with gastrointestinal and lung cancers being the most common (30.1% and 23.7%, respectively). The mean NRS rating reported by patients was 5.9 and for the VAS 4.9. Sixty patients (63.8%) preferred the NRS, 32 (34.0%) preferred the VAS, and 2 (2.1%) reported no preference. Patients who preferred the NRS reported a higher NRS rating than patients who preferred the VAS (mean NRS of 6.3 compared to 5.2, p = 0.0409). VAS ratings were higher among patients who preferred the NRS but the difference was not statistically significant (mean rating of 5.2 vs. 4.4, p = 0.1894). There were no differences in patient characteristics between the two groups. There was a moderate association between patients’ NRS and VAS ratings. The Pearson correlation coefficient was 0.653 (p < 0.0001). Conclusions: Majority of patients of all ages and both genders prefer NRS. Future studies involving larger number of patients and adding a question about the reason of scale preference may provide better understanding for scale preference.
Atypical femoral fracture in patients with malignant bone metastasis receiving denosumab therapy: Retrospective study.
Authors: Yukinori Ozaki , Takahashi Momoko , Nakajima Hiromichi , Ohki Ryosuke , Masuda Jun , Kondoh Chihiro , Miura Yuji , Tanabe Yuko , Takano Toshimi 
Published: November 2017

220 Background: While denosumab prevent skeletal-related events in patients with malignant bone metastasis, there are concerns that it may be associated with atypical femoral fracture (AFF). AFF in osteoporotic patients receiving denosumab is reported, but few data have been reported in the context of monthly denosumab therapy for patients with malignant tumor and bone metastasis. Methods: We reviewed the medical records and pharmacy database of patients who received denosumab at 120mg monthly for management of bone metastasis from May 2012 to June 2017 at our institution to analyze the incidence of AFF. To identify the risk factors and optimal management of AFF, we reviewed the clinical features and skeletal images of the patients. Results: We analyzed the data of 204 patients receiving a median of 7 doses (range; 1-60) of denosumab, and 150 (74%) patients received more than three times of denosumab. Four patients were diagnosed as AFF and incidence rate was 2.0%. Five limbs of the 4 patients were diagnosed as AFF and performed intramedullary nail fixation, and 2 limbs of the patients were diagnosed of atypical femoral stress reaction (AFSR) with surgical indication. These patients with AFF received 15, 44, 45 and 45 doses of denosumab, which showed higher doses of denosumab (median: 44.5 doses), compared to the patients without AFF or AFSR (median: 6 doses). Median age of the four patients was 59 (range: 50-66), and primary disease were breast cancer in three patients and non-small lung cell cancer in one patient. Conclusions: We experienced four AFF events among 204 patients receiving denosumab 120mg monthly and incident rate was 2.0%. More data are needed about the occurrence of AFF in these patients.
Analysis of retreatment after radiotherapy for bone metastasis at a safety net hospital.
Authors: Jennelle Richard Lester Stephen , Andrade Jacob , Williams Patrick , Bian Shelly , Ragab Omar Medhat , Yoo Stella , Pham Anthony , Lai Peter , Schechter Naomi , Ballas Leslie K. , Chang Eric L. 
Published: November 2017

223 Background: The effectiveness of single fraction radiotherapy in the treatment of bone metastasis is firmly established by multiple prospective randomized controlled trials. These trials have also indicated a retreatment rate that is significantly higher for patients treated with single fraction radiotherapy. The reason for this is unclear. The prior studies have confirmed that there are no differences in any objective or subjective measure of response or durability of response. One proposed explanation may be a conscious or subconscious impact of practice based workload accounting for adopting a single fraction treatment strategy that may lead to excess retreatment prescription. In other words, does a decrease in workload accounting due to single fraction treatment lead to an increase in retreatment rates? Our large safety net teaching hospital follows a practice model where department funding is independent of workload accounting. We retrospectively reviewed our data on the radiotherapy of bone metastasis to see if this practice model had any impact on our retreatment rates. Methods: Between October 2012 and June 2017, 225 patients received treatment for 385 target lesions. All referred patients’ entire radiotherapy history was included whether or not it occurred during the target period. 196 target lesions received single fraction treatment and 189 received multiple fractions. 27 target lesions were retreated once and a single target lesion was retreated twice. Results: Target lesions treated with a single fraction resulted in a retreatment rate of 7.7% while multiple fraction treatment resulted in a retreatment rate of 6.4%. This difference was not statistically significant by Chi-Square analysis. Conclusions: Our retrospective analysis confirms no difference in retreatment rates between single and multi-fraction treatment. The retreatment rate is in agreement with the published response rate and introduces a possible explanation for the discordant rates observed in the published literature. Further analysis involving multiple practice models would help further explore these findings.
Methadone as the initial long-acting opioid in children with advanced cancer.
Authors: Madden Kevin , Mills Sarah , Dibaj Seyedeh , Williams Janet L. , Liu Diane D , Bruera Eduardo 
Published: November 2017

224 Background: Methadone is an attractive medication for treating children with advanced cancer who have chronic pain, as it is the only long-acting opioid available as a liquid. This formulation allows for precise dosing that is not possible with the fixed dose of extended release tablets or transdermal patches. Additionally, it can be used in children unable to reliably swallow tablets. Many pediatric oncologists are concerned with methadone’s complex pharmacodynamics and pharmacokinetics, and so it is often relegated to being the long-acting opioid to use only after long-acting morphine, long-acting oxycodone, and fentanyl transdermal patches have proven to be ineffective in controlling pain. We believe that methadone has a role as the first long-acting opioid in children who have uncontrolled pain while only on immediate-release mu opioid agonists. Methods: Retrospective chart review of 52 consecutive patients referred to Pediatric Supportive Care for pain management started on methadone as their first long-acting opioid. Data collected at baseline and first follow up visit (F1) included child- and parent-reported outcomes for various physical and psychological symptoms, opioid side effects and other clinical data. All symptoms were rated on a 5 point scale: 0 (not at all), 1 (a little bit), 2 (kind of), 3 (quite a bit) and 4 (a lot). Results: Of 52 eligible patients, a majority (47, 90.3%) were assessed at F1. Reasons for not evaluating patients at F1 included death (3) (none died of cardiac arrhythmia or opioid related toxicity) and transfer of care to another facility (2). Pain as scored by the child was 3.6/4 at baseline and 1.8/4 at F1 (P < 0.0001). Pain as scored by the parent was 3.5/4 at baseline and 1.4 at F1 (P < 0.0001). A majority of patients (33, 70.2%) at F1 did not need a change in their methadone dose. A small number (10, 21.3%) needed an increase in their methadone dose due to inadequate pain control; a few (4, 8.5%) had a lower methadone dose but all were part of tapering methadone due to resolution of the original pain syndrome, not due to opioid toxicity. Conclusions: Initiation of methadone was effective and safe as the first long-acting opioid in children with pain due to advanced cancer.
Phase III study of palonosetron (PALO) given as 30-min IV infusion (IV inf) versus 30-sec IV bolus (IV bol) for prevention of chemotherapy-induced nausea and vomiting (CINV) associated with highly emetogenic chemotherapy (HEC).
Authors: Karthaus Meinolf , Szabò Péter , Voisin Daniel , Rizzi Giada , Ciuleanu Tudor 
Published: November 2017

227 Background: PALO (0.50 mg), a distinctive second-generation 5-HT3 receptor antagonist (RA), is a component of the oral fixed combination agent NEPA, the second component being the NK1 RA netupitant. Oral NEPA is approved for acute and delayed CINV prophylaxis after moderately (MEC) and HEC. This study was conducted in support of the NEPA IV formulation (0.25 mg PALO + 235 mg fosnetupitant) administered as a 30-min IV inf, currently under FDA review. Methods: Chemotherapy-naive patients (pts) with solid tumors were randomized (1:1) to receive a single 0.25-mg PALO as a 30-min IV inf or a 30-sec IV bol, 30 min before reference HEC (cisplatin; dacarbazine), with oral dexamethasone (20 mg [D1]; 8 mg BID [D2–4]) (NCT02557035). Primary objective: noninferiority (NI; lower limit of the 99% CI to be > –15% [prespecified NI margin]) in complete response (CR; no emesis/no rescue) in the acute (0–24 h) phase. Secondary objective: safety. Results: 440 pts (median age 59.4 y [25–79]; cisplatin: 97.3%; dacarbazine: 2.7%) were randomized to IV inf (n=225) or IV bol (n=215). Baseline characteristics were similar. Acute CR rate was 82.7% (IV inf) and 86.5% (IV bol), with risk difference of –3.8% (99% CI: –12.2; 4.7) meeting the primary objective of NI. Treatment-emergent AE and study drug-related AE frequency was similar in both arms (Table). One PALO IV inf patient with pre-existing cardiac symptoms, experienced 1 serious AE that eventually lead to death and was considered possibly study drug-related by the investigator. No G≥3 infusion site reactions occurred. No patient in IV inf arm had infusion interruptions. Conclusions: PALO IV inf was noninferior to IV bol in acute CINV prevention after receiving non-AC HEC. Safety profiles were similar. No specific infusion toxicities were observed. The results show that PALO 0.25 mg IV inf is appropriate for the NEPA IV formulation. Clinical trial information: NCT02557035. [Table: see text]
Cranial electrotherapy stimulation for the management of depression, anxiety, sleep disturbance, and pain in patients with advanced cancer: A preliminary study.
Authors: Yennu Sriram , Kang Duck Hee , Hwu Wen-Jen , Padhye Nikhil S , Masino Charles , Liu Diane D , Dibaj Seyedeh , Williams Janet L. , Lu Zhanni , Bruera Eduardo 
Published: November 2017

229 Background: Cranial Electrotherapy Stimulation (CES) is a safe modulation of brain activity for treating depression, anxiety, insomnia, and pain. However, there are no published studies in patients with advanced cancer (ACP).The aim of the study was to determine the feasibility and preliminary efficacy of a 4-week CES intervention on depression, anxiety, sleep disturbance, and pain scores. Concurrent salivary biomarker studies were conducted. Methods: In this one group open label pre- and post-intervention study with a 4-week CES intervention, ACP’s with one or more of four moderate intensity (≥3/10) ESAS symptoms (depression, anxiety, sleep disturbance, and pain) were eligible. Adherence (0-100%), satisfaction rates(0-10), and safety were assessed. ESAS, HADS, PSQI, BPI, and salivary levels (cortisol, alpha amylase, CRP, and IL-1 beta and IL-6) were assessed from baseline to week 4. Results: 33/38(87%) completed the CES. Median (IQR) adherence for days with 60 min CES use and satisfaction scores were 93(89-100)% and 10(9-10) respectively. CES use was safe (no grade 3 or higher adverse events). HADS anxiety (p < 0.001), HADS depression (p = 0.024), ESAS anxiety (p = 0.001), depression (p = 0.025), BPI pain (p = 0.013), PSQI daytime dysfunction (p = 0.002), and Medication use (p = 0.006) scores improved after 4 week CES treatment. There was no significant change in the salivary cortisol, alpha-amylase, CRP, IL-1β, and IL-6 levels after 4 weeks of CES. Conclusions: In this preliminary study we found that the use of cranial Electrotherapy stimulation (CES) was safe and feasible in ACP. The use of CES was associated with significant improvement of depression, anxiety, pain, and sleep scores. These findings support further studies of CES in ACP for symptom control.
Randomized trial of a smartphone mobile app for adherence to oral chemotherapy.
Authors: Jacobs Jamie M. , Pensak Nicole , Nisotel Lauren Ellen , Fishbein Joel N , MacDonald James J , Ream Molly , Fuh Charn-Xin , Buzaglo Joanne S. , Muzikansky Alona , Lennes Inga Tolin , Safren Steven A. , Pirl William F. , Temel Jennifer S. , Greer Joseph 
Published: November 2017

230 Background: As patients with cancer are increasingly prescribed oral chemotherapy, they share greater responsibility for ensuring adherence and monitoring side effects. The aim of this study was to test the effect of a smartphone mobile app to improve adherence and symptom management in patients prescribed oral chemotherapy. Methods: From 2/15 to 12/16, 181 patients with diverse cancers prescribed oral chemotherapy at an urban cancer center were randomized to receive either the smartphone mobile app or standard care. The mobile app included a medication treatment plan with alerts, symptom reporting module, education library, and cancer-specific resources. The primary outcome was adherence, measured by electronic pill cap (MEMS) and self-report (Morisky Medication Adherence Scale; MMAS). To assess symptoms, mood, and quality of life, participants completed the MD Anderson Symptom Inventory, Hospital Anxiety & Depression Scale (HADS); and Functional Assessment of Cancer Therapy-General (FACT-G) at baseline and 12 weeks. General linear models were used to assess intervention effects on patient outcomes. Results: Study groups did not differ across outcome measures from baseline to week 12, except patients in the mobile app group had less of a reduction in social well-being (FACT-G) over time (Mean Diff = 1.67, 95% CI = -3.12, -0.21, p = .025). Secondary analyses showed that baseline adherence (MMAS) and anxiety (HADS) were moderators of intervention effects on self-reported and electronically monitored adherence. Among patients who reported adherence problems, those assigned to the mobile app had better average MEMS adherence (Mean Diff = -22.30, 95% CI = -42.82, -1.78, p = .034) compared to standard care. Similarly, among patients with higher baseline anxiety, those in the mobile app group had better average MEMS adherence (Mean Diff = -16.08, 95% CI = -31.74, -0.41, p = .044) and reported fewer adherence problems on the MMAS at 12 weeks (4.3% vs 32%, OR = 0.06, 95% CI = 0.003, 0.96, p = .047) compared to standard care. Conclusions: A patient-centered, smartphone mobile app designed to improve adherence to oral chemotherapy may be especially useful for patients with certain risk factors, such as those struggling with adherence or anxiety. Clinical trial information: NCT02157519.