bluuebunny/crossref_metadata_2025 huggingface dataset:
Result of the feasibility study of lidocaine (LDC) for peripheral venous pain induced by oxaliplatin (L-OHP).
Authors: Sakai Daisuke , Uemori Miwako , Sugiura Takashi , Kudo Toshihiro , Boku Miwa , Tanizaki Keiko , Kato Aya , Mizushima Tsunekazu , Doki Yuichiro , Mori Masaki , Satoh Taroh , Hayashi Taro
Published: September 2018

e21624

Background: For the patients with colorectal cancer, CapeOx or SOX, combination of L-OHP with oral fluoropyrimidines Capecitabine or S-1, is commonly used in clinical practice. These regimens, different from FOLFOX, do not necessarily require central venous port placement and can be administered via peripheral vein. However, peripheral vascular pain induced by administration of L-OHP was discussed. Methods: LDC was concomitantly administered through the lateral duct of drip route from 30 minutes before to end of L-OHP administration, to patients with colorectal cancer who are to be administered L-OHP (100 mg/m2 or more) via the peripheral vein for the first time. LDC dose was set at two levels of 0.5 (Level 1) and 1.5 (Level 2) mg / kg / Hr. Safety, symptoms of pain and pharmacokinetics of LDC were evaluated. The DLT criteria were (1) an allergic reaction of Grade 2 or higher, (2) non-hematological toxicity of Grade 3 or more related to LDC, (3) cessation of administration of L-OHP or LDC, (4) higher than 5 mcg / mL of blood concentration of LDC. Results: A total of nine patients were enrolled (Level 1: 3, Level 2: 6). No DLTs were observed. The average Cmax of LDC was 0.4 (range: 0.3 - 0.5) mcg/ml at Level 1 and 1.3 (0.5 - 2.3) mcg / ml at Level 2. In the pain assessment (VAS score), in Level 1, 2 cases did not feel pain, 1 case was 3/10. In Level 2, there were no pain in 4 cases and 2/10 in the remaining 2 cases. Conclusions: To alleviate vascular pain caused by peripheral intravenous administration of L-OHP, concomitant administration of LDC could be safe and effective. Clinical trial information: UMIN000011393.
The benefits of patient-centered patient registries.
Authors: Durborow Michelle , Aljallad Kathrena , Call Jerry , Menos Mildred , Scherzer Norman J.
Published: September 2018

e21625

Background: Created in 2001, The Lift Raft Group GIST Patient Registry has always put the patient at the heart of its work. Those contributing data are not merely study participants but people in need of help. In 2017, the newest evolution of the Registry debuts- GIST/PRIME, an interactive desktop/mobile application that serves both the patient and doctor to track treatment efficacy and disease progression over time rather than the traditional single survey input. Methods: The Registry operates on an SQL cloud based platform under an IRB informed consent process. Incoming members provide their full disease history. Examples of data collected include: Demographic, primary tumor site, date(s) of diagnosis, initiation of treatment, dosage, and response to treatment. Outcomes are based upon response to drug therapy. Research analysis is supported by the platform’s filterable, queryable and auto-calculating fields as well as unique features such as treatment lines which chart therapy history to investigate potential correlation between mutational status, drug treatment and order of drug taken. Results: The traditional registry structure only provides a one-way benefit- from patient to registry. GIST/PRIME seeks to remedy this by providing a clear set of benefits and user-friendly features back to patients: The Dashboard displays Registry demographics and how the patient relates others within the system. Based on entered data, this dashboard can also calculate Risk of Recurrence and provide education on treatment and mutational types; Input and editing of Diagnosis, Evaluation and Treatment; push notifications; The GISTORY- An exportable, printable document that provides a comprehensive summary of a patient’s GIST medical history, helping facilitate efficient communication between patient and doctor. Conclusions: The idea of reframing a patient registry as a tool which can provide as much benefit to its members as it does to the researchers who analyze its data is overdue. By committing to a patient-centered structure and style, registry members are more deeply engaged over time, providing richer data that is not limited to a single drug or place of treatment.
Clinical outcome and characteristics of patients with cervical cancer submitted to renal replacement therapy.
Authors: Reis Diego , Rocha Eduardo , Ishida Tatiane Cristine
Published: September 2018

e21627

Background: Cervical cancer is the 2nd most prevalent and 4th cause of cancer-related death in Brazil among women. It may cause renal failure due to tumoral growth, the treatments, among other causes. Purpose: To evaluate the clinical outcome and the risk of death in patients with cervical cancer hospitalized submitted to hemodialysis, to describe the clinical characteristics of these patients. Methods: Retrospective observational study. Patients diagnosed with cervical cancer, hospitalized, submitted to renal replacement therapy were identified in a single institution (n = 92). Risk of death was estimated using Kaplan-Meier analysis. The Cox proportional hazards regression model was used to determine the risk of death on the basis of: cancer staging, disease activity, Performance status at admission, oncological surgery before hemodialysis subgroup. Results: 92 patients with cervical cancer hospitalized were submitted to intermittent hemodialysis between January 2007 and December 2008. Data was available for all the 92 patients. Median age at diagnosis 47.8 years (25.4-95.1), 73.9% was diagnosed stage III/IV, 95% had disease progression/ active disease before hemodialysis. 84 patients (91%) were dead at the moment of analysis (Cut-off date 30/03/2010), median interval between first hemodialysis and death 1.1 months (0-24.8). The main cause of death was postrenal kidney failure (82.6%). In multivariate analysis, stage II/III/IV (compared with stage I) and disease progression/active disease were the only independent prognostic factors associated with increased risk of death (HR = 3.149; 95% CI, 1.765 to 5.610; P = .001 and HR = 4.205; 95% CI, 1.002 to 17.65; P = .05). Conclusions: Women with advanced disease and active disease/ disease progression have a significant increased risk of death compared with those with stage I, stable disease/ disease in remission. Prospective studies are warranted to investigate the benefit hemodialysis in patients with cervical cancer.
A novel integrative medicine educational program for radiation oncology patients: Feasibility and patient-reported outcomes.
Authors: Fakhoury Kareem , Stavas Mark J.
Published: September 2018

e21629

Background: Integrative medicine uses complementary health approaches (CHAs) to improve wellness. Many patients use CHAs to manage acute and late toxicities of radiotherapy (RT). However, few patients disclose CHA use to their radiation oncologist. Patients acknowledge a need for improved education on CHAs and have shown interest in attending a hospital-based educational program. Here we assess the feasibility of implementing such a program and the associated patient-reported outcomes, including intention to disclose CHA use and patient satisfaction. Methods: A structured curriculum was designed as a collaboration between an academic institution’s integrative medicine center and radiation oncology department. Four one-hour lectures covered topics of meditation, yoga, massage therapy, and nutrition, each led by a topic expert. Lectures included didactic and interactive components. Individuals over age 18 and actively receiving RT were recruited by nurses, radiation therapists, and a designated study team member in the waiting room. Pre- and post-lecture surveys were used to assess patient characteristics, CHA use disclosure, satisfaction, and qualitative feedback. Results: 43 surveys were completed. The patient sample was 47% female, median age 63. The majority had breast or prostate cancer (60%). Of about 100 patients receiving RT each day, 5 to 7 attended each lecture. 36% of participants had disclosed their use of CHAs before the lecture; 67% intended to disclose their use after the lecture. 98% felt the lecture enhanced their patient experience with a median agreement of 8 on a 9-point Likert scale. Conclusions: This program is the first to increase satisfaction and CHA use disclosure. Patients expressed interest in learning simple, convenient, and effective tools to abate acute toxicities, rather than focus on chronic symptoms of remission and recovery. However, patient recruitment could not be effectively integrated into the clinical workflow. Attendance was limited by timing, transportation, and performance status. To increase reach and minimize cost, we suggest investigating a program that is integrated into the clinic visit or available in an online format.
Pre-injection wheel running preserves mobility in a rodent model of paclitaxel neurotoxicity.
Authors: Hile Elizabeth , Kostereva Nataliya , Marra Kacey
Published: September 2018

e21640

Background: Peripheral neurotoxicity (PN), a common side-effect of paclitaxel (Ptx) chemotherapy, can reduce quality of life through persistent balance/gait dysfunction, and even shorten survival by limiting therapy. Exercise before chemo, or ‘prehabilitation’ (prehab), seems to protect cardiac and cognitive function, but few have studied mobility, or identified gait parameters most sensitive to PN, to inform larger neuroprotection work. Aims of this preclinical, proof of concept pilot were to identify 1) if pre-Ptx wheel running preserves mobility, 2) key gait parameters for the Ptx-PN phenotype, 3) potential mechanisms for prehab neuroprotection. Methods: Adult female Lewis rats were randomized to 3 arms under equivalent housing: sedentary before injection of vehicle (SedSham), sedentary before 36 mg/kg Ptx (SedPtx), or prehab wheel running 60 min, 5 days/wk X 5 wks pre-Ptx (ExPtx). Outcomes were blinded mobility observation and DigiGait spatiotemporal parameters at baseline, before & after injection, and at euthanasia, with peripheral nerves (sural, sciatic, tibial, fibular) harvested for immunohistochemistry and quantitative histomorphometry with GAP43 (neuroplasticity) & S100 (Schwann) antibodies. Consistent with small pilot design, analyses were primarily descriptive comparisons. Results: A single blinded assessor correctly identified group assignment for 7 of 8 (87.5%) videotaped rats by post-injection mobility observation alone, identifying slowness, frequent paw contact/ reduced forepaw exploration, and flattened paws as Ptx-PN phenotype. Paw changes were confirmed by post-hoc Digigait image comparison. 'Percent propulsion' emerged as a key gait parameter in sensitivity analysis with a prehab non-responder. Levels of S100 appear lower in SedPtx group nerves compared to ExPtx and SedSham animals. Conclusions: Mobility deficits after Ptx are often attributed to peripheral somatosensory changes rather than neuromotor dysfunction, yet these preclinical results echo our growing anecdotal clinical observations. While preliminary, both suggest greater attention to distal strength and motor function after Ptx exposure.
Symptoms and health related quality of life in patients receiving matched therapy.
Authors: Williams Kirstin Anne , Williams Casey B. , Rojas Luis , Starks David , Krie Amy K. , Leyland-Jones Brian , Bergquist-Beringer Sandra
Published: September 2018

e21648

Background: Genomic sequencing is increasingly being used to select targeted agents that are matched to molecular alterations. Potential differences in symptom occurrence and severity as well as health related quality of life (HRQOL) between patients who receive matched therapy and those who do not receive matched therapy have not been previously explored. Methods: Existing data from the records of patients with breast or gynecologic cancer receiving outpatient care were used for this descriptive correlational research study. Descriptive statistics and multiple linear regression analyses were performed to address the study aims. Symptom occurrence and severity and HRQOL were measured with the previously validated Therapy-Related Symptom Checklist (TRSC) and HRQOL – Linear Analogue Self Assessment (HRQOL-LASA) respectively. A higher total TRSC score indicated high symptom occurrence and severity; a higher total HRQOL-LASA score indicated a high quality of life. Results: Patients receiving matched therapy had lower mean TRSC scores ( M= 14.7, SD= 10.1) compared to patients receiving not matched therapy ( M= 16.1, SD= 11.6). Patients receiving matched therapy had higher mean HRQOL-LASA scores ( M= 48.1, SD = 7.5), compared to patients receiving not matched therapy ( M= 45.4, SD= 9.1). Mean ratings were higher for patients receiving matched therapy on each individual HRQOL domain. Therapy type (matched, not matched) was not significantly associated with TRSC scores (B = -3.0, p= 0.18) or HRQOL scores (B = 2.0, p= 0.18) after controlling for person and disease factors. Conclusions: On average, patients receiving matched therapy had lower symptom occurrence and severity scores and higher HRQOL scores when compared to patients who were not receiving matched therapy. Type of therapy (matched, not matched) was not significantly associated with symptom or HRQOL scores. Study findings provide initial data about the symptom experience and HRQOL and for patients receiving matched therapy.
Differences in global toxicity burden among patients and care providers during initial chemotherapy for breast cancer.
Authors: Rowland John Christopher , Hershman Dawn L. , Kalinsky Kevin , Crew Katherine D. , Cheung Ying Kuen , Lee Shing Mirn
Published: September 2018

e21649

Background: To better assess the safety of new drugs in cancer clinical trials, a measure of the overall toxicity burden is essential. We propose a novel tool for eliciting an overall toxicity burden score from physicians, nurses and patients, and compare these scores at baseline and after initial chemotherapy. Methods: Sixty patients starting therapy for breast cancer were enrolled prospectively from 2013 to 2015. Before and after starting therapy (cycle 2 day 1), a global toxicity burden score (TBS) was elicited from each patient using a scale from 0 to 10 based on the burden of their disease and therapy on their daily life, with 10 indicating more burden. After toxicities were collected using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), the treating physician and nurse completed an identical questionnaire independently. Baseline TBS, and pre- and post-treatment differences in TBS, number of CTCAE reported and overall health from the EORTC QLQ-C30 (higher indicating better health) were compared using paired t-tests. Results:Out of the 59 evaluable patients, the average age was 54 years, 1 was male, 55% were white, 41% Hispanic, 16% stage III or IV, and 59% received adjuvant therapy. Patients reported higher TBS at baseline compared to clinicians (mean (SD): patients = 3.10 (2.78), nurses = 1.26 (1.55), physicians = 0.90 (1.33); p < 0.001). Moreover, while post-treatment patient reported outcomes were worse, they were not significantly different (mean difference (SD): TBS = 0.27 (2.74) p = 0.48; overall health status = -5.13 (21.53) p = 0.09). However, the number of toxicities and clinicians’ TBS increased significantly post-treatment (mean difference (SD): number of toxicities = 3.61 (2.71) p < 0.001; physicians = 1.65 (1.47) p < 0.001; nurses = 1.58 (1.41) p < 0.001). Conclusions: The proposed tool for eliciting overall toxicity burden is simple and suggests that clinicians underestimate disease burden at baseline, and while the increase in number of toxicities after treatment is reflected in increased clinician reported burden, it is less apparent in patient reported outcomes. Future research should evaluate new measures of burden and toxicities over time.
Partial splenic embolization in chemotherapy-induced thrombocytopenia: A retrospective analysis with long term follow-up.
Authors: Procaccio Letizia , Schirripa Marta , Bergamo Francesca , Dadduzio Vincenzo , Finotto Silvia , Menichetti Alice , Ziampiri Stamatia , Carandina Riccardo , Loupakis Fotios , Lonardi Sara , Zagonel Vittorina , Aliberti Camillo
Published: September 2018

e21654

Background: Chemotherapy-induced thrombocytopenia (CIT) may result in a chemotherapy (CT) dose delay or reduction, thus affecting dose density and intensity. Historically, partial splenic embolization (PSE) has been performed to improve hematologic parameters related to hypersplenism. In this study we reviewed our institutional experience with PSE for gastrointestinal cancer (GI) experiencing CIT. Methods: A retrospective analysis of GI cancer patients with splenomegaly undergoing PSE was performed. Mean PLT (platelet) count was collected at the following time points: before CT start; at nadir pre-PSE; 1 week before PSE (pre-PSE); 4 weeks after PSE (post-PSE); and at the nadir after CT reintroduction post PSE. Time to CT restart after PSE, time to recurrent CIT, periprocedural lab values and adverse events were recorded. Wilcoxon test was adopted to exploratively compare PLT count before and after PSE. Results: 11 patients underwent PSE, 5 with colorectal, 3 with pancreatic and 3 with biliary cancer, 73% had metastatic disease. Baseline PLT count before initiation of CT was 146 x109/L (range, 81-255 x 109/L). PLT count at nadir pre-PSE was 60 x109/L (range, 44-82 x 109/L), and pre-PSE PLT count was 78 x109/L (range, 62-99 x 109/L). Post-PSE PLT count improved significantly ( 132 x 109/L; range, 67-172 x109/L) compared with nadir pre-PSE (p = 0.003). The mean hospital stay was 1 day. Post-procedure abdominal pain occurred in 3 patients. All patients resumed CT and mean time to CT re-start after PSE was 43 days (range, 4-193 d). All patients exhibited recurrent thrombocytopenia. PLT count at nadir after PSE was 54 x 109/L (range, 28-78 x 109/L) and occurred at a mean of 169 days after PSE (range, 37-664 d) No differences were observed when comparing CIT at nadir pre and post PSE (p = 0.447). All patients experienced CT dose delay and 82% of them experienced dose reduction after PSE. Conclusions: Our findings underline that PSE is safe and effective to achieve short-term improvement of CIT and resumption of CT in GI patients. However, PSE does not sustain long-term adequate PLT count. Further studies may help guide patient selection by identifying characteristics that allow a sustained improvement in CIT.
Effectiveness and safety of LMWH treatment in patients with cancer diagnosed with nonhigh-risk venous thromboembolism (VTE): Results of the Turkish observational study (TREBECA).
Authors: Ozaslan Ersin , Ozkan Metin , Cicin Irfan , Benekli Mustafa , Kocer Murat , Uysal Mukremin , Oksuzoglu Berna , Isikdogan Abdurrahman , Cubukcu Erdem , Elkiran Emin Tamer , Dane Faysal , Aliustaoglu Mehmet , Sevinc Alper , Karaoglu Aziz , Ulas Arife , Dogu Gamze Gokoz
Published: September 2018

e21656

Background: Venous thromboembolism (VTE) is one of the most important causes of death in cancer patients, with VTE risk being 4-7 times higher among these patients compared to normal population. TREBECA is an observational study on cancer outpatients with low risk VTE treated with LMWH. Methods: Patients were treated by medical oncologists in Turkey at 15 sites, where they were enrolled and followed-up for a period of 12 months. Each center used their own treatment protocol. Primary endpoints were efficacy and the time to a change inVTE status (dissolution of thrombosis). The doses of LMWHs have been calculated according to patients’ body weights based on the dosage scheme and administered subcutaneously once or twice daily. Results: Data for 250 patients who met the study inclusion criteria were examined and analyzed. Of the included patients; 239 patients (95.6%) completed their Day 15 visit, 176 (70.4%) completed their Month 3 visit, 130 (52.0%) completed their Month 6 visit, and 91 (36.4%) completed the entire study. The mean age of the patients was 60.2 ± 13.7, while 53.2% (n = 133) of the patients were women. Colorectal (21.2%), lung (16.8%) and breast (14.8%) cancers were the most common forms of cancer. One hundred thirty-three patients were treated with enoxaparin, 112 patients were treated with bemiparin and 5 patients were treated with tinzaparin. Bemiparin resulted thrombosis resolution in more patients than enoxaparin, during day 15, month 3 and month 6 visits (table 1; p < 0.05). Conclusions: The observation that bemiparin is more effective in resolution of thrombosis was noteworthy. Thrombosis could not be effectively treated within the first 15 days in a significant number of patients, but could effectively be treated in most patients by Month 3. We can conclude that a treatment of at least 3 months is appropriate for cancer patients, even among those who are at low risk for venous thromboembolism. [Table: see text]
Does oncologist productivity impact goals of care discussions?
Authors: Pintova Sofya , Smith Cardinale B. , Adelson Kerin B. , Gonsky Jason Parker , Egorova Natalia , Franco Rebeca , Bickell Nina A.
Published: September 2018

e21675

Background: Oncologists are pressed to care for higher volumes of advanced cancer patients. Interviews with oncologists revealed their concern that goals of care (GoC) discussions take time. We studied the impact of oncologists’ productivity on their conduct of meaningful GOC discussions with patients. Methods: At academic, municipal and rural hospitals, we recruited & randomized solid tumor oncologists & their newly diagnosed advanced cancer patients with <2 year prognosis to participate in a RCT testing a coaching model of communication skills training. All oncologists were encouraged to have GoC discussions at the visit after imaging to restage. Patients are surveyed after that post-imaging visit. We define GoC discussions as patient report that their doctor talked about preferences for cancer treatment and clarified things most important to them given their illness. We measure quality of GoC discussions by patients’ rating. Productivity was measured by work revenue value units (wRVUs) per hour for the day each oncologist saw the study patient post-imaging. Results: We enrolled 22/25 oncologists (88%); to date 77 patients completed surveys. Productivity did not vary significantly by hospital though oncologists generated greater wRVUs at the municipal hospital (p=0.2203). Overall, 36% of patients report having a high quality GoC discussion. There was no significant relationship between level of productivity and conduct of high quality GoC discussion. Multivariate model controlling for hospital and intervention found no relationship between productivity and conduct of high quality GoC discussion. Conclusions: Despite concerns about the time required to conduct GoC discussions, we found that productivity did not affect oncologists’ ability to conduct high quality GoC discussions nor did conduct of a GoC reduce productivity. The prevalence of high quality GoC discussions was low. [Table: see text]
Supportive care and symptom burden in patients with myeloproliferative neoplasms.
Authors: Gowin Krisstina L. , Millstine Denise , Kosiorek Heidi E. , Langlais Blake , Huberty Jennifer , Eckert Ryan , Mesa Ruben A.
Published: September 2018

e21684

Background: Pharmacologic therapy stabilizes hematologic counts and splenomegaly in myeloproliferative neoplasms (MPN), however only partial symptom improvement typically occurs. Evidenced-based supportive care interventions are needed, however data is limited in patients with MPNs. Methods: Patients were recruited internationally via social media. Informed consent and online self-report surveys (Qualtrics) were completed capturing patient demographics, disease specific data, supportive care utilization, and symptom burden via MPN-SAF TSS. ANOVA, chi square tests, and Wilcoxon rank sum tests methods were applied. Results: Patients:1087 patient surveys were consented. Of these, 858 had 10 or more responses. There were 338 essential thrombocytosis (ET), 188 myelofibrosis (MF), 315 polycythemia vera (PV), and 17 other. In MF: DIPSS risk categories included low (8%), Int-1 (19%), Int-2 (29%), high (12%), and unknown (32%). Supportive care:The most frequently utilized therapies were aerobic activity in 442 patients (51.5%), massage in 244 (28.4%), yoga in 220(25.6%), nutrition in 216 (25.1%), and strength training in 204 (23.7%). Symptom association: Among all respondents, aerobic activity (p=<0.001), massage (p=<0.001), yoga (p=0.02), and strength training (p=<0.001) was associated with lower symptom burden by the MPN-SAF TSS however, nutrition was not (p=0.10). In ET and PV subgroups, yoga intervention was no longer statistically significant (p=0.35, p=0.14). In the MF subgroup, no intervention was found to be significant in any risk category. Conclusions: Supportive care with aerobic activity, massage, yoga, and strength training is associated with improved symptom burden in patients with MPN. Further studies are needed to understand the benefits of such therapies. [Table: see text]
Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in lung cancer patients receiving carboplatin-based therapies.
Authors: Weinstein Cindy , Jordan Karin , Green Stuart , Khanani Saleem A. , Beckford-Brathwaite Elizabeth , Vallejos Waldimir , Pong Annpey , Noga Stephen Joseph , Rapoport Bernardo
Published: September 2018

e21685

Background: Chemotherapy-induced nausea and vomiting (CINV) is a distressing symptom of cancer treatment; in lung cancer, carboplatin is commonly used. In a post hoc analysis, we explored prevention of CINV in lung cancer patients with a single-day triple-antiemetic fosaprepitant (FA) regimen compared with a standard 3-day control regimen. Methods: This was a phase 3, global, randomized, double-blind, parallel-group study in adults scheduled to receive an intravenous (IV) dose of ≥1 moderately emetogenic chemotherapy (MEC) on treatment day 1 (NCT01594749). Subjects were randomly assigned 1:1 to a control or FA regimen. The control regimen consisted of 8 mg oral ondansetron, 20 mg dexamethasone, and IV saline as placebo before the first dose of MEC on day 1, and 8 mg oral ondansetron 8 hours after the first dose and every 12 hours on days 2 and 3. The FA regimen consisted of the same dose of oral ondansetron on day 1, along with 12 mg dexamethasone and a single dose of 150 mg IV FA before the first dose of MEC on day 1, with no additional prophylactic antiemetic beyond day 1. The primary end point was complete response (CR; no vomiting or rescue medication) in the delayed phase (25-120 hours). Results: Overall, 1000 subjects were included in the intention-to-treat population (FA: n = 502; control: n = 498). The primary end point was met ( P < 0.001; FA vs control). In a subset of 254 subjects with lung cancer (71% male), 129 in FA regimen and 125 in control regimen, most (98%) received carboplatin-based chemotherapy. CR in the delayed phase was achieved by 80.6% in the FA group and 74.4% in the control group (difference, 6.2%). More subjects had no vomiting episodes in the FA (85.3%) vs control (78.4%) groups within the delayed phase (difference, 6.9%), and overall time-to-first vomiting episode was longer for subjects in the FA group. Adverse events (AEs) were similar between groups: overall AEs occurred in 57.7% and 54.8%, and serious AEs occurred in 12.3% and 12.1% in the FA and control groups, respectively. No serious AEs were considered related to study medication. Conclusions: A single-day IV FA regimen is effective for preventing CINV in patients with lung cancer receiving carboplatin. Clinical trial information: NCT01594749.
Systematic review and individual patient data based meta-analysis of palonosetron trials for chemotherapy induced nausea and vomiting.
Authors: Okada Yuki , Oba Koji , Furukawa Naoto , Komatsu Yoshito , Kosaka Yoshimasa , Okita Kenji , Yuki Satoshi , Celio Luigi , Aapro Matti S.
Published: September 2018

e21688

Background: Several clinical trials have evaluated the need for corticosteroid-containing antiemetic regimens on the days after the first 24 hours to control delayed chemotherapy-induced nausea and vomiting (CINV) during moderate emetogenic chemotherapy (MEC) or anthracycline and/or cyclophosphamide (AC)-containing chemotherapy. Methods:We conducted systematic review using research databases and trial registries for any randomized controlled trials reporting CINV outcomes for a single 1-day-dexamethasone (D1 group) containing antiemetic regimen in chemotherapy-naive adult patients scheduled to receive a MEC or AC-containing chemotherapy, compared with additional dexamethasone on days 2 and 3 (D3 group). We also gathered the individual patient data (IPD) from each study investigator. The primary endpoint was complete response (CR: no vomiting and no rescue antiemetics) in the 5-day study period. Secondary efficacy end points were CR rates in 0–24 h and CR rates in 24–120 h; complete control in the overall, acute, delayed periods. An IPD meta-analysis was conducted to quantify the pooled risk differences between D1 group and D3 group and its interaction with patient characteristics using a fixed effect model. Results: Of 887 articles screened, 5 eligible studies were identified comprising 1194 patients, all enrolled in the meta-analysis. Overall, D1 group was not significantly inferior to D3 group in CR rate as well as CC rate [pooled risk difference in CR rate -1.5%, 95% confidence interval (CI) -7.1–4.0%; in delayed CR rate -2.4%, 95% CI -7.7–2.9%]. There was no significant interaction between dexamethasone regimen and patient characteristics (sex, age category ( < 60 or 60 years), and alcohol consumption). Conclusions: These results strongly suggest that the dexamethasone-sparing regimen is not associated with a significant loss in overall antiemetic control in an adult patient undergoing MEC or AC-containing chemotherapy, irrespective of patient baseline characteristics. These data contribute to simplify antiemetic regimens and spare many patients from the potential side-effects of multiple-day corticosteroids.
Randomized, single-blind, crossover study to assess the pharmacokinetic and pharmacodynamic bioequivalence of CHS-1701 to pegfilgrastim in healthy subjects.
Authors: Glaspy John A. , O'Connor Paula G. , Tang Hong , Finck Barbara
Published: September 2018

e21693

Background: CHS-1701 is a proposed biosimilar of pegfilgrastim, a pegylated form of recombinant human granulocyte colony stimulating factor approved for decreasing infection in patients receiving myelosuppressive anticancer drugs associated with febrile neutropenia. This multi-center, randomized, single-blind, 3-sequence, crossover study in healthy subjects assessed bioequivalence of CHS-1701 to pegfilgrastim with regard to pharmacokinetics (PK) and pharmacodynamics (PD). Methods: Subjects were randomized to 1 of 3 treatment sequences; each included 1 dose of CHS-1701 (6-mg) and 2 doses of pegfilgrastim (6-mg) separated by ≥28 days. Primary PK endpoints were area under the curve from 0 to infinity (AUC0-∞) and maximum concentration (Cmax). PD endpoints were maximum absolute neutrophil count (ANCmax) and ANC area under the curve (ANC AUCs). Bioequivalence was demonstrated if the 90% confidence interval (CI) for the geometric mean ratio (GMR) of CHS-1701 to pegfilgrastim was within 80-125% for the endpoints. Results: 122 subjects were randomized and treated. Baseline characteristics were comparable between treatment groups. Median age was 29.5 (range 18-45). PK bioequivalence criteria were met for Cmax (GMR = 105.0; 90% CI 95.5, 115.4) and AUC0–∞ (GMR = 97.5; 90% CI 88.6, 107.2). PD bioequivalence criteria were met for ANCmax (GMR = 99.6; 90% CI: 96.2, 103.2), ANC AUC0–last (GMR = 96.7; 90% CI: 92.2, 101.4), and ANC AUC0–480 (GMR = 99.8; 90% CI: 97.7, 102.0). Adverse events (AEs) occurred in 76.0%, 76.6%, and 73.1% of subjects during the CHS-1701, first pegfilgrastim, and second pegfilgrastim dosing periods across treatment sequences, respectively. Investigator-designated treatment-related AEs occurred in 71.9%, 71.2%, and 62.8% of subjects, respectively, and most commonly included back pain (47.9%, 42.3%, 33.3%) and headache (33.3%, 41.4%, 34.6%). There were no treatment-related serious AEs. Conclusions: This study established the bioequivalence of CHS-1701 to pegfilgrastim with respect to PK and PD. There were no unexpected safety findings, and the two treatments displayed similar safety profiles. Clinical trial information: NCT02650973.
Patient and physician satisfaction with analgesic treatment in Southeast Asia (SEA): Findings from the analgesic treatment for cancer pain in Southeast Asia (ACE) study.
Authors: Moon Hanlim , Thinh Dang Huy Quoc , Sriraj Wimonrat , Mansor Marzida Binti , Tan Kian Hian , Yusak Suhana , Kurnianda Johan , Nguyen Yen Phi , Ong-Cornel Annielyn Beryl , Hadjiat Yacine , Javier Francis
Published: September 2018

e21698

Background: Adequate dosing of analgesics is important for optimum cancer pain control & quality of life (QoL). To understand current attitudes toward analgesic treatment for cancer pain in SEA, the ACE study explored patient & physician satisfaction with pain control in 6 SEA countries. Methods: This cross-sectional observational study included 465 adult outpatients prescribed analgesics for cancer pain for ≥1 month in Indonesia, Malaysia, Philippines, Singapore, Thailand, & Vietnam. Pain intensity, sleep disturbance, QoL, satisfaction with pain control, & physicians’ assessment of adequacy of analgesics were recorded via questionnaires. Current analgesic doses prescribed were extracted from medical records. Results: Most patients (84%) had stage 3 or 4 cancer. While 91% were prescribed opioids, mean reported pain intensity was 4.1 (0/no pain, 10/worst possible pain) & most had problems with sleep (55%) & QoL (problems with pain/discomfort [82%], usual activities [66%] & anxiety/depression [56%]). 60% of patients were satisfied with their pain control status & 30% found it acceptable. Physicians more often reported dissatisfaction with patients’ pain control status compared with patients (21% vs 10%). Patient-physician concordance in satisfaction with pain control was low (weighted Kappa 0.36; 95% CI 0.30-0.43). More than 1 in 4 physicians (29%) assessed prescribed analgesics to be “inadequate” for pain control. Median daily dose prescribed in oral morphine equivalents was 30 mg for both morphine & tramadol. Of the SEA countries included, prescribed doses of opioids were generally lower in Indonesia & higher in Vietnam. Conclusions: The results highlight the complexity of managing cancer pain in SEA. Despite unrelieved pain, sleep disturbance & QoL issues, many patients still reported satisfaction with pain control. Notably, physicians expressed dissatisfaction more frequently than patients. These findings suggest a need for all-round pain status assessment (including pain intensity, sleep disturbance, QoL) & improved patient-physician communication about analgesic treatment expectations, pain control & adverse effects.
A randomized, double-blind, placebo-controlled study of the safety and efficacy of olanzapine for the prevention of chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy.
Authors: Jeon So Yeon , Han Hye Sook , Bae Woo Kyun , Park Moo-Rim , Lee Sang-Cheol , Go Se-Il , Yun Hwan Jung , Ryu Hyewon , Im Yong-Jin , Song Eun-Kee
Published: September 2018

e21699

Background: Olanzapine was found to be effective for preventing acute and delayed emesis in patients receiving highly emetogenic chemotherapy by randomized phase 3 study. However, there is limited data for the efficacy of olanzapine combined with palonosetron and dexamethasone in patients receiving moderately emetogenic chemotherapy (MEC). Methods: We conducted randomized, double-blind, placebo-controlled study to determine whether olanzapine could reduce the frequency of CINV and improve quality of life (QOL) in patients receiving palonosetron and dexamethasone for the prophylaxis of MEC induced nausea and vomiting. Two groups received either 10 mg of olanzapine orally or matching placebo daily on days 1 through 4. The primary end point was the complete response (no emesis and no use of rescue medication) for the acute phase (0-24 hours after chemotherapy). Secondary end points included the complete responses for the delayed (24-120 hours) and overall phase (0-120 hours), proportion of significant emesis (VAS ≥ 25 mm) for overall phase, use of rescue medications, and effect on QOL by Functional Living Index-Emesis (FLIE) questionnaire. Results: Fifty-six patients were randomized and fifty-four patients were evaluable (29 assigned to olanzapine, and 25 to placebo). The complete response rate was not significant between olanzapine and placebo group in the acute (96.5% vs. 88.0%, P = 0.326), delayed (69.0% vs. 48.0%, P = 0.118), and overall phase (69.0% vs. 48.0%, P = 0.118). However, the percentage of patients with significant emesis (17.2% vs. 44.0%, P = 0.032) and the use of rescue medications (0.03±0.19 vs. 1.88±2.88, P = 0.002) were significantly lower with olanzapine than with placebo in the overall phase. Furthermore, olanzapine group experienced a better QOL than the placebo group, as reported on the FLIE questionnaire (P = 0.015). Conclusions: Olanzapine in addition to palonosetron and dexamethasone significantly improved the management of emesis and QOL among previously untreated patients receiving MEC, although the efficacy was limited to reduce the frequency of CINV. Clinical trial information: NCT02400866.
Integrating a touchscreen-based brief geriatric assessment in older adults with multiple myeloma.
Authors: Nathwani Nitya , Mohile Supriya Gupta , Lipe Brea , Carig Karen , DiGiovanni Laura , Davis Agnes , Wujcik Debra , Hurria Arti , Wildes Tanya Marya
Published: September 2018

e21703

Background: Multiple myeloma (MM) is a disease of older adults (OAs) with > 60% of diagnoses and nearly 75% of deaths occurring in patients > 65 years old (YO). Geriatric Assessment (GA) is associated with toxicity and survival in OAs with MM, but not routinely used in practice. This project pilot tests a tablet-based modified Geriatric Assessment (mGA) that presents compiled GA results, including (the Palumbo) frailty score, to clinicians at a treatment decision-making visit in a single screen dashboard. Methods: In this multisite ongoing study, 210 patients with MM ≥65 YO facing a decision point for care will complete a mGA that includes the Charlson Comorbidity Index (CCI), Katz Activity of Daily Living (ADL) Score, and Lawton Instrumental Activity of Daily Living (IADL) Score prior to meeting with a physician. mGA results, including composite frailty score, are provided to physicians at the start of a visit. Results: Thirty-six patients have been enrolled to date; enrollment continues. Participants are 69% (n = 25) white, 64% (n = 23) male, and mean age of 72 YO (range 65-87). Most (74%, n = 20) currently receive ≥1 therapy and have few co-morbidities (CCI median 1, SD 1.95, range 0-8); 57% require assistance with IADLs and 37% require assistance with ADLs. Based on Palumbo score, 36% of participants were frail (n = 13), 33% intermediate (n = 12), and 31% fit (n = 11). Providers report mGA results influenced treatment decision (54%, n = 28) and frailty score was the most frequently cited result to impact treatment decision-making (61%, n = 39). The most common way the mCGA influenced decision-making was to reduce dose/dose intensity (25%, N = 8). Clinicians on average spent 5 minutesreviewing the mGA results. Patients reported an average of 7 minutes to complete the survey, most independently (83%, n = 30), and were satisfied with the electronic program overall (80%, n = 29), including how easy it was to use (88%, n = 32). Conclusions: Preliminary data support feasibility, usability, and acceptability of the tablet-based mGA and that frailty score influences provider decision-making ≥50% of the time. Future analyses will explore the relationship of the mGA with toxicity, dose modification and/or treatment discontinuation in OAs with MM.
Differences in body composition between patients with early or metastatic breast cancer (BC).
Authors: Strulov Shachar Shlomit , Deal Allison Mary , Weinberg Marc , Williams Grant Richard , Nyrop Kirsten A , Choi Seul Ki , Benbow Julia M. , Muss Hyman B.
Published: September 2018

e21707

Background: There is growing evidence in oncology that skeletal muscle (SM) loss, known as sarcopenia, can be identified from routine computed tomography (CT) imaging and used to predict increased chemotherapy toxicity, mortality, and other adverse clinical outcomes (Shachar-EJC, 2016, Shachar-CCR, 2016). The contributions of age-related and cancer-related loses in SM at diagnosis remains poorly understood. This study compares CT-derived measures of SM at the time of diagnosis in patients with early BC (EBC) versus metastatic BC (MBC) patients to investigate the impact of metastatic cancer on SM. Methods: Body composition measures were compared between patients with EBC receiving adjuvant chemotherapy and MBC initiating first line palliative chemotherapy. Measures were derived from analysis CT scans of L3 lumbar segments using radiological software (ABACS). Measures include: skeletal muscle area (SMA), density (SMD), index (SMI = SMA/height ^2), and integrated density (SMID = SMI x SMD). Sarcopenia was defined as SMI < 41(Martin-JCO, 2013). Lean body mass (LBM) was calculated (kg) = [(L3 Muscle measured by CT (cm2) × 0.3) + 6.06]) (Prado-CCR, 2009). Body surface area (BSA) was calculated using the Mosteller formula. T-tests (continuous) and Chi-squared tests (categorical) compared variables between groups; multivariable linear regression models controlled for age and body mass index (BMI). Results: MBC patients (n = 40) were older than EBC (n = 151) (56 vs 49 years, p < 0.001). Mean BMI and BSA were similar in both groups (29.0 vs 28.8, p = 0.84; 1.87 vs 1.86 m2, p = 0.55). After adjusting for age and BMI, SMI (41.3 vs 44.7 cm2/m2, p = 0.009), SMD (29.8 vs 36.4 Hounsfield Units, p < 0.0001), SMG (1250 vs 1612, p < 0.0001), and LBM (39.3 vs 41.9 kg, p = 0.024) were significantly lower in the MBC group. The MBC group included significantly more sarcopenic patients (58% vs 31%, p = 0.0016). Conclusions: Although BMI and BSA were similar in EBC and MBC patients, SM measures showed significant differences. MBCs had lower LBM, SMI, and SMD. More advanced BC was associated with higher proportions of sarcopenia. Further research is needed to explore interventions in sarcopenic patients in order improve outcomes in women with both EBC and MBC.
Factors impacting time to engraftment in patients with high-risk neuroblastoma following autologous stem cell transplant.
Authors: Hillier Kirsty , Krance Robert , Foster Jennifer Haunani
Published: September 2018

e22008

Background: Neuroblastoma is the most common extra-cranial solid tumor of childhood, with overall survival for high-risk patients (HRNBL) near 50%. The outcomes of HRNBL have improved significantly with high dose chemotherapy followed by autologous stem cell rescue (ABMT). Data about factors influencing the rate of hematopoietic recovery following ABMT in HRNBL is lacking in the literature. Methods: This is a retrospective chart review of patients with HRNBL treated at Texas Children’s Hospital from October 2011 - November 2016. Neutrophil engraftment was considered the first of three consecutive days with post-transplant neutrophil count > 500 cells/uL. Red blood cell and platelet engraftment were considered at a hemoglobin > 8g/dL and platelets > 20,000/uL three days after the last transfusion. Race and conditioning regimen were analyzed using one-way ANOVA; amount of infused cells was analyzed using Pearson correlation coefficients; chemotherapy delay and bone marrow (BM) involvement after cycle 2 of induction chemotherapy were analyzed using independent sample t-tests. Results: The study included 17 males and 8 females with a median age at diagnosis of 3 years. 15 patients were Caucasian, 4 African-American, 5 Hispanic, and 1 Asian. The mean dose of infused CD34+ cells was 3.44x108cells/kg. 16 patients received conditioning therapy with carboplatin/etoposide/melphalan, 7 received busulfan/melphalan, and 2 received thiotepa/cyclophosphamide. Race was found to be significant for hemoglobin engraftment (p < 0.001). There were trends toward significance for conditioning regimen and neutrophil engraftment (p = 0.079), presence of delays in induction chemotherapy due to hematologic toxicity for platelet engraftment (p = 0.069) and BM involvement after cycle 2 of induction chemotherapy for hemoglobin engraftment (p = 0.12). Conclusions: Knowing the barriers for timely engraftment may help develop interventions for future patients. Race significantly impacted hemoglobin engraftment. Conditioning regimen, delays in induction chemotherapy, and BM involvement after cycle 2 of induction chemotherapy trended towards significance and need to be validated in a larger dataset.
SOX2 as a target for immunotherapy of pediatric gliomas.
Authors: Vasquez Juan , Huttner Anita , Zhang Lin , Marks Asher , Chan Amy , Baehring Joachim M. , Kahle Kristopher , Dhodapkar Kavita M.
Published: September 2018

e22012

Background: New treatments are needed to improve outcomes for pediatric gliomas. Immune checkpoint inhibitors are effective therapies in tumors with a high mutation burden that express multiple neo-antigens. However, for pediatric tumors that carry few mutations, there is a need to identify new antigenic targets of anti-tumor immunity. SOX2 is an embryonal stem cell antigen implicated in the biology of glioma initiating cells. Expression of SOX2 by pediatric glial tumors, and the capacity of the immune system in these patients to recognize SOX2, has not been studied. Methods: We examined the expression of SOX2 on paraffin-embedded tissue from pediatric glial tumors (n = 30). The presence of T cell immunity to SOX2 was examined in both blood and tumor-infiltrating T cells using antigen-dependent cytokine and T cell proliferation assays (n = 15). The nature of tumor-infiltrating immune cells in glial tumors (n = 4) was analyzed using single cell mass cytometry. Results: SOX2 is expressed by tumor cells but not surrounding normal tissue in all low grade gliomas (n = 15), high grade gliomas (n = 7), ependymomas (n = 3) and in 60% of oligodendrogliomas (n = 5). T cells against SOX2 can be detected in blood and tumor tissue in 33% of patients. CD4 and CD8 tumor infiltrating T-cells display a higher proportion of PD-1 expression compared to circulating T cells (p < 0.05). Glial CD4 and CD8 T cells are enriched for tissue resident memory phenotype (TRM; CD45RO+, CD69+, CCR7-) and the expression of PD-1 is primarily on these TRM cells (p < 0.05). A subset of CD4 and CD8 TRM cells also co-express multiple inhibitory checkpoints including PD-L1 and TIGIT. Glial tumors also contain NK cells with reduced expression of lytic granzyme (p < 0.05). Conclusions: Our data demonstrate in vivo immunogenicity of SOX2, which is specifically overexpressed on pediatric glial tumor cells. Our data also suggest that the TRM subset of tumor-infiltrating T cells may be key targets for immune checkpoint blockade, and harnessing tumor immunity will likely require the combined targeting of multiple inhibitory checkpoints. Future efforts to target SOX2 with dendritic cell vaccines combined with immune checkpoint blockade could provide effective tumor immunity and improve outcomes in pediatric brain tumors.