bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal physical activity assessment in post-surgical gynecologic cancer patients.
Authors: Gorzelitz-Liebhauser Jessica , Costanzo Erin S. , Spencer Ryan J. , Rumble Meredith E. , Rose Stephen L. , Cadmus-Bertram Lisa
Published: September 2018

e21582

Background: Physical activity is a key determinant of health, and exercise can be effective for decreasing anxiety and depression and improving quality of life in cancer survivors. The primary aim of this study was to report the trajectory of physical activity over time for post-operative gynecologic cancer patients. The secondary aim was to identify correlates of total physical activity over time. Methods: The study population included patients who underwent surgery for endometrial (n = 80) or ovarian (n = 43) cancer and wore an accelerometer for a 3-day period at 1 week, 1 month and 4 months after surgery. Accelerometer data were captured during all waking hours and were transformed into categories of light, moderate and vigorous intensity physical activity. The outcome of interest was total minutes of moderate to vigorous intensity physical activity (MVPA) collected over the three day period at each time point, analyzed using a linear mixed effect model approach, assessing the correlates of age, body mass index (BMI), self-rated health, laparotomy vs. laparoscopic (endometrial only) and neoadjuvant chemotherapy yes/no (ovarian only). Results: Mean age was 58.8 ± 10.1 years with mean BMI of 35.5±10.3 kg/m2. Over each three-day period, patients performed 7 ± 12 minutes of total accumulated MVPA at 1 week, 20 ± 41 minutes of total MVPA at 1 month, and 25 ± 36 minutes at 4-months post-surgery (p = 0.01). Federal guidelines recommend approximately 70 minutes of moderate intensity activity over a three-day period to collect 150 minutes of moderate activity a week. Better self-rated health at baseline was associated with increased activity over time (p = 0.02). BMI, age, type of surgery or use of neoadjuvant chemotherapy did not predict physical activity in patients of either disease site. Conclusions: Physical activity increased over time for endometrial and ovarian cancer patients. Self-reported health at baseline was also positively associated with increased moderate-vigorous physical activity over time. There is insufficient evidence to show that BMI significantly contributes to changes in moderate-to-vigorous physical activity over time. Future research should address barriers to activity and novel interventions.
Impact of fertility preservation by ovarian stimulation on breast cancer outcomes.
Authors: Wang Ying , Lee Shaina , Camateros Pierre , Perdrizet Kirstin Ann , Yokom Daniel , Warner Ellen , Roberts Jeffrey , Lohrisch Caroline A.
Published: September 2018

e21588

Background: Chemotherapy and hormone therapy results in potential ovarian toxicity and delay in child-bearing among women of reproductive age with breast cancer. Whether short term ovarian stimulation is safe is not well studied. We examined the effects of short-term ovarian stimulation on patients’ breast cancer recurrence rates. Methods: Women diagnosed with localized breast cancer between 2005 and 2011 at any one of five cancer centres and referred to a reproductive endocrinologist in British Columbia, Canada, were identified from a central database. Clinical, pathological, treatment, and outcome characteristics were compared for patients who did and did not undergo ovarian stimulation prior to systemic cancer treatment. Results: Seventy-seven patients were included: median age was 33, all were ECOG 0/1, 31 (40%) had lymph node involvement, 62 (81%) had estrogen receptor (ER) positive disease, and 18 (23%) had HER2 positive disease. Thirty-four (44%) women underwent ovarian stimulation: they were more likely to receive chemotherapy than patients who declined ovarian stimulation (p = 0.001). Age, number of existing children, radiation, and hormonal treatments were not significantly associated with decision to undergo ovarian stimulation (p > 0.05). After a median follow-up of 3.7 years, 7 (21%) patients who pursued ovarian stimulation and 9 (21%) patients who did not experienced disease recurrence. There was no association between ovarian stimulation and rate of local or distant breast cancer recurrence (p = 0.658). Conclusions: We did not find a harmful effect of short term ovarian stimulation on breast cancer recurrence rates. Limitations include short follow-up, a small sample size, and few relapses. Patients who received chemotherapy were more likely to pursue ovarian stimulation, suggesting that patients were well informed about the negative impact on fertility of chemotherapy and of the importance of fertility preservation prior to potentially gonado-toxic treatments.
A longitudinal, multimodal approach to characterizing chemotherapy-induced peripheral neuropathy.
Authors: Ramnarine Sabrina , Dougherty Patrick M. , Williams Linda J , Gourley Charlie , Fallon Marie T
Published: September 2018

e21595

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a complex, dose-limiting toxicity impacting prognosis and quality of life. The optimal approach to identification and assessment remains unclear. This study aims to prospectively characterize the development and trajectory of CIPN using a combination of patient-reported outcomes (PROs) and objective Quantitative Sensory Testing (QST) measures in gynaecological, colorectal and lung cancer patients receiving neurotoxic platinum and/or taxane-based chemotherapy. Methods: Patients (n = 33, mean age 60.8) were evaluated at baseline prior to chemotherapy, during (every 3 weeks) and post-treatment every 3 months up to 1 year. Assessments at each time point included: PRO (EORTC QLQ-CIPN20 questionnaire) and QST measures (thermal and mechanical detection and grooved pegboard test). Statistical modelling using repeated measures analysis by patient was conducted. Results: Significant and parallel changes were observed in PROs and QST measures over time. Total EORTC score (sensory, motor and autonomic) increased in severity from baseline at all time points, peaking at 3 months post-treatment (34.8% increase; p < 0.0001) and persisting at 1 year (17.9% increase; p = 0.01). Every increase by one point in EORTC sensory score over time corresponded with an elevation in QST parameters: warm detection threshold (upper limb; p = 0.02 and lower limb; p = 0.03) and mechanical detection threshold, MDT (upper limb; p = 0.04 and lower limb; p = 0.02). Equally, rising total EORTC and motor score were related to increasing MDT in the upper limb p = 0.02 and p = 0.003 respectively. A delay of one second taken to complete the grooved pegboard test (dominant hand) was linked to a proportional increase in EORTC motor score (p = 0.01). Conclusions: Associations are shown here amongst PROs and QST parameters providing an opportunity to quantify and synthesize objective with subjective measures of neuropathy in CIPN patients. This may have potentially informative implications to underlying mechanisms of CIPN symptom burden, contributing to a more comprehensive clinical picture and allow stratification of patients by phenotype severity. Additional studies are warranted.
Characteristics and predictors of pain in patients with newly diagnosed and relapsed acute leukemia (AL).
Authors: Shaulov Adir , Rodin Gary , Rydall Anne , Popovic Gordana , Schimmer Aaron David , Le Lisa W , Zimmermann Camilla
Published: September 2018

e21633

Background: AL is a hematopoietic stem cell malignancy associated with substantial morbidity and mortality. The prevalence, correlates and causes for pain in this population have not been well studied. We present the results of a large cross-sectional study of pain in individuals with AL. Methods: Patients with newly-diagnosed or recently-relapsed AL admitted to a large tertiary cancer center completed the Memorial Symptom Assessment Scale (MSAS, which has subscales of prevalence, severity, frequency and distress, with ratings of 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe). Demographic information, and disease and treatment variables were recorded. Two raters completed chart reviews in duplicate (with discussion of discordant results) for patients with severe pain (MSAS severity ≥3/4) to assess the site of pain. Results: A total of 362 patients were recruited from January 2008 to October 2013: 249 (68.8%) with AML, 80 (22.1%) ALL and 33 (9.1%) APL. Of these, 326 (90.1%) were newly diagnosed and 36 (9.9%) had relapsed disease; 346 (95.6%) were treated with (re)induction chemotherapy. Of 360 who completed the MSAS, pain was reported in 174 (48.3%), of whom 34.4% scored ≥3/4 on severity, 43.1% on frequency, and 44.3% on distress related to the pain. On multivariable analysis, patients reporting pain were more likely to be younger (OR 0.98 old vs young, p < 0.001), and to have ALL (OR 0.57 AML vs ALL, p < 0.05); duration of illness, gender, education, income and treatment intensity were not associated with pain. Pain was correlated with difficulty sleeping, worrying, difficulty concentrating, and feeling sad, nervous or irritable (all p < 0.001). Of the 60 patients reporting severe pain (≥3/4), its site was identified in 53 (88.3%). The most common sites were oropharynx (29.7%), head (18.9%), abdomen (14.9%) and musculoskeletal (12.2%). Only 1.1% (4/362) of the cohort was referred to the palliative care/symptom control team over the month prior to or following assessment. Conclusions: Pain is a frequent and distressing symptom in patients with newly diagnosed or relapsed AL. Further research is needed to assess the efficacy of supportive care interventions in this population.
A comparison of liver cancer and lung cancer patients at two Veteran Affairs Medical Centers.
Authors: Kothadia Sejal , Wang Zhen , Lee Sarah , Chang Victor Tsu-Shih , Wang Yucai , Park Yeun-Hee Anna , Olson Ellen , Klein David , Leaf Andrea Nadine , Hwa Stephanie , Zhong Fengming
Published: September 2018

e21642

Background: Little is known about palliative care for liver cancer. In this study, we examined palliative care for liver cancer and lung cancer patients. Methods: In an IRB approved protocol, we reviewed medical records of patients diagnosed with liver cancer who were seen by the palliative care service between 2006 and 2012 at 2 VA medical centers, and matched them to patients with lung cancer by year, KPS, and stage. Veterans were compared by symptom prevalence with the CMSAS and by palliative care interventions. Statistical analyses were performed with SAS Studio Version 3.5. Results: We analyzed a total of 138 male patients at 2 VA centers; 69 with lung cancer and 69 with liver cancer. The mean age in both groups was 65 years and 60% of patients self-identified as a minority. There was a high prevalence of symptoms in both groups. Symptom prevalence differed significantly between liver and lung cancer pts for weight loss and dyspnea at one site, and for feeling drowsy, constipation, at the other site. These differences disappeared in a pooled analysis. During palliative care evaluation, more lung cancer patients received treatment for constipation (n = 44 in lung, 29 in liver, p = 0.0107) and dyspnea treatment (n = 37 in lung, 22 in liver, p = 0.0167). More patients with lung cancer were evaluated by physical therapy (n = 41 in lung, n = 28 in liver, p = 0.0276) and psychiatry (n = 31 in lung, n = 20 in liver, p = 0.032). Conclusions: Differences between lung and liver cancer patients’ symptom prevalence and treatment by palliative care can vary by site. This reinforces the importance of local surveys of symptom prevalence . Further studies should be replicated in other sites.
Cancer related insomnia and wireless technology: A pilot study.
Authors: O'Connor Brenda , Ui Dhuibhir Pauline , Walsh Declan
Published: September 2018

e21645

Background: Cancer related insomnia (CRI) includes difficulty with sleep onset, maintenance or non-restorative sleep. CRI is common with prevalence up to 95%. Consequences include cognitive dysfunction, fatigue, increased hospitalisation and lost work productivity. Early detection may help. CRI remains under-investigated as objective assessment has needed specialised laboratories. Mobile technology may provide a solution. This study aimed to determine the feasibility and acceptability of a wireless bedside monitor (SleepMinder [ResMed Sensor Technologies Ltd, Dublin]) to evaluate CRI. Methods: A prospective observational study recruited 10 consecutive hospice inpatients (IP) and 20 consecutive community participants (CP) with cancer. Participants used a wireless non-contact bedside sleep monitor for 3 consecutive nights. Three insomnia features were examined (sleep onset, maintenance, early awakening). Computerised algorithm-generated metrics were compared to visual inspection of the monitor sleep/activity report. Acceptability questionnaires were completed by patient, nurse and family. Results: The device successfully recorded sleep patterns in all 30 participants. No technical difficulties were experienced. IP: Mean age was 63 +/- 9 years. 7/10 had one or more insomnia features with delayed sleep onset most common. The monitor over-estimated Sleep Latency (77% nights), Duration (77% nights) and Final Awakening (63% nights). CP: Mean age was 64 +/- 10 years. 15/20 had one or more insomnia features with poor sleep maintenance most common. The monitor overestimated Sleep Duration (62% nights) and Final Awakening (45% nights). Lower levels were noted in CP as they spent less time in bed. Patients, nurses and family members reported high (100%) device acceptability. Conclusions: A wireless bedside monitor effectively measured sleep in seriously ill cancer patients in both inpatient and outpatient settings without the use of a sleep laboratory High reliability and acceptability supports routine clinical use Sensitivity of wakefulness detection was reduced as the device incorrectly identified sleep during awake but motionless periods Concurrent use of sleep diary and a monitor is recommended for comprehensive assessment
Olanzapine versus aprepitant in the prevention of chemotherapy induced nausea and vomiting (CINV) in breast cancer patients.
Authors: Mukesh S , M Sathya , Jk Akshay
Published: September 2018

e21670

Background: Olanzapine has been shown to be a safe and effective agent for the prevention of CINV. This study aims to compare olanzapine with aprepitant in the prevention of CINV. Methods: This study included breast cancer patients receiving doxorubicin 60mg/m2 and cyclophosphamide 600mg/m2 chemotherapy. Female patient; age, ≥ 18; chemotherapy naïve; no nausea/ vomiting in the past 24 hours were included. Patients with seizure disorder, brain metastasis, prior use of antipsychotic agents and hypersensitivity to olanzapine were excluded. Patients were randomized into two groups. Olanzapine group received tab olanzapine 10 mg on day 1 to 3. Aprepitant group received tab.aprepitant 125mg on day 1 and 80mg on days 2-3. Both groups received inj palnosteron 0.25mg, inj dexamethasone 8mg on day 1. Use of rescue therapy for nausea or vomiting was permitted. The primary end point of the study was complete response (CR) for nausea that is no nausea in the acute (within 24 hours), delayed (days 2-5), and overall periods (0-120 hours). Secondary endpoint was CR for vomiting and no use of rescue drugs in all periods. Beginning with the first day of chemotherapy and daily through day 5, patients were asked to record daily episodes of nausea using a visual analogue scale from 0 to 10, with 0 indicating no nausea and 10 indicating a maximal level of nausea. They were asked to record daily episodes of vomiting (number and time) and the utilization of rescue therapy. Results: A total of 84 patients (42 in each arm) were evaluated and consented for the study. The median age 48 years; range 29-80; ECOG PS - 0, 1. CR for nausea was 84% for the acute period , 58% for the delayed period and 56% for the overall period for the olanzapine group. CR for nausea in aprepitant group was 69% acute period, 55% delayed period, and 55% for the overall period. CR for vomiting was 91% acute; 74% delayed; 70% overall period for olanzapine group. CR for vomiting in aprepitant group was 91% acute; 83% delayed; 83% overall period. There were no Grade 3 /4 toxicities. Conclusions: Olanzapine is better in the prevention of nausea. However aprepitant is better in the prevention of vomiting. Combination of these two agents needs to be studied in future studies.
Use of granulocyte colony stimulating factor (GCSF) in patients receiving highly myelosuppressive chemotherapy for breast cancer.
Authors: Kornelsen Emily , Cheung Winson Y.
Published: September 2018

e21677

Background:We hypothesized that GCSF use may be suboptimal in the real world despite prior research that shows prophylaxis with GCSF can reduce neutropenic fevers and hospitalizations. Our aims were to characterize patterns of GCSF use in a population-based cohort of breast cancer patients receiving highly myelosuppressive chemotherapy and to describe outcomes and predictors associated with appropriate GCSF prophylaxis. Methods:Patients diagnosed with breast cancer from 2008 to 2012, seen at any 1 of 5 comprehensive cancer centers in a Canadian province, and treated with chemotherapy that posed > 20% risk of neutropenic fever were reviewed. Associations between GCSF use and 1) patient and physician factors and 2) treatment outcomes, including rate of neutropenic fevers, were analyzed using regression models. Results:We included 805 women: median age was 52 (IQR 44 to 61) years, 40% reported smoking, 52% used alcohol regularly, 64% were ECOG 0, and 24% had private health insurance. In this cohort, 330 (41%) patients were given GCSF. Among those treated with GCSF, 132 (40%) and 198 (60%) individuals received GCSF as primary and secondary prophylaxis, respectively. Overall, neutropenia was noted in 467 (58%) cases while neutropenic fever was experienced by 161 (20%) patients. When compared to those who did not use GCSF, patients who used GCSF experienced a lower rate of neutropenia (14% vs. 61%, p < 0.01) and a decreased incidence of neutropenic fever (8% vs. 23%, p < 0.01). In regression models, patients lacking extended medical coverage (32% vs. 49%, p = 0.02), poor performance status (30% vs. 55%, p = 0.03), and those who were evaluated at non-teaching institutions (25% vs. 69% p < 0.01) were less likely to receive GCSF. Patients seen at non-teaching institutions were also given primary GCSF prophylaxis less frequently (16% vs 59%, p < 0.01) than those at teaching centers. Conclusions:GCSF prophylaxis was associated with improved neutropenia-related outcomes in the real world. Despite evidence-based recommendations, use of GCSF remains suboptimal in this population-based cohort of breast cancer patients receiving highly myelosuppressive chemotherapy.
Association of risk of febrile neutropenia (FN) with docetaxel in prostate cancer (PC) patients: A meta-analysis of published phase II-III trials.
Authors: Maria Blazquez Arroyo , Merida Garcia Antonio , Lora David , Bernard Brandon David , David Lorente , Manneh Kopp Ray , Sepúlveda Juan Manuel , Castellano Daniel , Sweeney Christopher , De Velasco Guillermo
Published: September 2018

e21683

Background: Reported rates of FN with docetaxel (DTX) in PC patients are variable. This creates uncertainty regard the use of granulocyte colony-stimulating factor primary prophylaxis (G-CSF) in this setting. We conducted a meta-analysis of randomized clinical trials to determine the relative risk (RR) of FN in patients receiving DTX. Methods: To perform this analysis we systematically searched in PUBMED and MEDLINE database the following terms: “DTX”, “randomized clinical trial” and “prostate cancer” only for articles published between January 1996 and August 2016. Phase II-III clinical studies comparing DTX to non-DTX control arms (best supportive care [BSC] including non-cytotoxic therapy or mitoxantrone) for PC were included. The meta-analyses were performed by computing RRs with 95% confidence intervals (CI) using fixed-effects model with the Mantel-Haenszel method. Results: Seven studies (N = 5088 patients) were included. The global incidence of FN in patients treated with DTX was 10.7%. The RR of FN was higher in patients receiving DTX compared to patients did not receive DTX (RR 16.8 [95% CI 10.7; 26.4] p < 0.0001). 6.6% of patients with metastatic castration resistant prostate cancer (CRPC) treated with DTX developed FN, the RR of FN with DTX compared to mitoxantrone was 28.6 (95% CI 5.6; 145.1). 12.4% of patients with hormone-sensitive prostate cancer (HSPC) treated with DTX developed FN, the RR of FN was 15.3 (95% CI 9.6; 24.6) compared to BSC. There was no statistically significant differences in the rate of FN according to the hormone sensitivity (HSPC vs CRPC) (p = 0.7). In most studies the use of G-CSF was at the discretion of the investigator. Conclusions: This meta-analysis shows that DTX is associated with a significant increase in the relative risk of FN in patients with PC. The effectiveness of primary prophylactic G-CSF in this setting has not been fully established. The incidence reported here does not meet the threshold recommended by ESMO and ASCO guidelines for the use of prophylactic G-CSF. Special attention should be given to high risk groups for FN, including elderly patients and those with bone marrow involvement or previous radiotherapy/chemotherapy.
Prevalence of critical malnutrition (CMN) in patients enrolling on phase I/II (P1/2) clinical trials.
Authors: Jain Rishi , Handorf Elizabeth , Khare Vipin , Chertock Yana , Hall Michael J.
Published: September 2018

e21700

Background: Cancer therapies undergo evaluation in P1/2 trials, frequently in patients (pts) with disrupted caloric intake, weight loss, and other adverse effects of cancer on physical and psychological functioning. CMN and sarcopenia may increase treatment related toxicity (TRT) due to acquired pharmacokinetic variability and altered drug metabolism. Little is known about the prevalence of CMN among pts enrolling on P1/2 trials, its association with abnormal physical and psychological functioning, and its role in mediating TRT. Methods: Pts initiating a P1/2 trial were recruited. Study acceptance rate was > 95%. Pts had a comprehensive nutritional assessment using the validated PG-SGA, a short, 3-5 minute tool that evaluates multiple nutritional domains [symptom burden, functional status, metabolic stress and physical exam (muscle/fat status)]. CMN is defined as a PG-SGA score of ≥ 9. Distress, anxiety, depression and physical activity were also measured. BMI and albumin were extracted from the chart. Statistical significance was determined by Fisher’s exact test. Results: 54 pts (85% P1) were enrolled. CMN was identified in 39%. Pts with gastrointestinal (GI) cancers were more likely to have CMN than non-GI cancers (75% vs 24%, p = 0.001); otherwise, CMN rates were not different by age ( < 60 vs 60+), gender, race, or trial phase (1 vs 2). CMN was also associated with number of lines of therapy, but was surprisingly less common among patients with > 2 therapies compared to those with 0-2 (29% vs 57%, p = 0.051). Strong associations of CMN to distress (p = 0.028), depression (p = 0.020) and sedentary lifestyle (p = 0.012) were also seen. Clinical “red flags” of MN such as low BMI ( < 25) and low albumin ( < 3.5) had poor sensitivity (66.7% and 33.3%) and specificity (57.6% and 78.8%) for CMN. Correlation of CMN to TRT is underway. Conclusions: CMN is prevalent among P1/2 trial pts, notably in those with GI cancers and with fewer lines of therapy, and is associated with physical inactivity, distress and depression. BMI and albumin are poorly predictive of CMN. Undiagnosed CMN may, through multiple pathways, increase the vulnerability of pts on P1/2 studies to TRT. Comprehensive nutritional assessment of P1/2 pts should be considered.
Trajectories of anxiety among breast cancer patients treated with chemotherapy pre- and post-chemotherapy compared to healthy controls: A nationwide multicenter study.
Authors: Paterson Carly Lynn , O'Mara Ann M. , Heckler Charles E. , Kipnis Victor , Kamen Charles Stewart , Ontko Mary , Schmidt Karen , Mitchell Jerry W. , Janelsins Michelle Christine
Published: September 2018

e21711

Background: A diagnosis of breast cancer (BC) elicits a myriad of concerns for women. Treatments are complex, often with multiple components, including chemotherapy. This study describes the trajectory of anxiety among BC patients treated with chemotherapy compared to healthy controls. Methods: This prospective observational study of breast cancer and lymphoma patients is being conducted through the National Cancer Institute Community Oncology Research Program (NCORP). For this analysis, women diagnosed with stage I-III BC and age-matched healthy controls were assessed using the State Trait Anxiety Inventory (STAI) at baseline prior to chemotherapy, 1-month and 6-months post-treatment. Baseline characteristics were compared using Welch’s t-test and chi-squared tests, and proportions of participants reporting anxiety between groups were examined at each time point. Linear mixed models (LMM) were used to compare anxiety trajectories over time, accounting for relevant baseline clinical, medical and demographic factors. Results: Among 945 participants, including 581 BC patients and 364 controls, the average age was 53 years, 91% were White, and 98% were non-Hispanic. Compared to controls, more BC patients reported anxiety scores > 40 at baseline (35% vs. 13%), 1-month (31% vs. 16%), and 6-months (30% vs. 19%), indicating potentially clinically significant anxiety. While BC patients’ anxiety decreased after an apex at baseline, it remained significantly higher than controls’ anxiety at each time point (all p < 0.001), and LMM analysis identified group and group by time interactions for each follow-up (all p < 0.001). Among all participants, predictors of increased anxiety included younger age, post-menopausal status, lower baseline cognitive function and higher baseline depressive symptoms. Conclusions: BC patients reported higher anxiety than controls at all time points, providing further insight into the trajectory of anxiety pre- and post-chemotherapy. Research into optimal timing of assessment and appropriate interventions to minimize anxiety burden in this population is warranted. Clinical trial information: NCT01382082.
Efficacy of treatments in children with relapsed/refractory acute lymphocytic leukemia (r/r ALL).
Authors: Martin Amber L , Thomas Simu K. , Cota Mariana , Hao Yanni , Zhang Younan , Turner Monica
Published: September 2018

e22001

Background: Pediatric ALL is the most common childhood leukemia, 20% of children relapse after initial complete response (CR) to first-line treatment and the 5-year overall survival (OS) of pediatric r/r ALL patients is only 30%. A systematic literature review (SLR) and meta-analysis (MA) were conducted to determine the effects of treatments for pediatric r/r ALL. Methods: EMBASE, MEDLINE, and CENTRAL databases were searched from 01/01/2000-12/31/2016 using keywords for r/r ALL paired with terms for pediatric patients and relevant treatments to identify studies reporting efficacy and safety data. Proceedings from 2015-2016 oncology conferences were also searched. Statistical analysis was limited to studies with comparable patient populations and treatment regimens. Random-effects MA of single-arm data were performed to determine the OS rate at 6 and 12 months, median OS, and the rate of CR (timepoint not reported) for pediatric r/r ALL patients treated with clofarabine + cyclophosphamide + etoposide (CCE). Results: The studies included in the review were heterogeneous and just five of the 46 studies identified by the SLR were similar enough for MA in terms of outcomes and populations (median age 8-14 years, median 2 prior lines of therapy). All five studies were single-arm studies evaluating CCE, a treatment with a pooled 6-month OS of 43.5% (95% CI: 32.6% - 55.1%), 1-year OS of 26.7% (95% CI: 17.5% - 38.3%), and pooled median OS of 5.2 (95% CI: 3.2 – 8.6) months. The CR rate was 43.2% (33.7% - 53.3%) across the five studies (timepoint not reported), and the rate was comparatively higher when analysis was limited to those with B-cell immunophenotype (56.3% [95% CI: 22.5% - 85.1%]). Conclusions: This is the first SLR and MA to be conducted on pediatric r/r ALL to date. Available evidence was heterogeneous and MA were only possible for single-arm trials examining CCE. Survival is poor in this population, as just over a quarter of patients receiving CCE were alive at 12 months, with median OS less than 6 months. CR rates were more promising but the lack of data on timepoint of assessment make the results difficult to interpret. New treatments are needed to better manage patients in this r/r population.
Advances in the approach to treatment of bilateral retinoblastoma: 26-year experience.
Authors: Kebudi Rejin , Tuncer Samuray , Bay Buyukkapu Sema , Sencer Serra , Gorgun Omer , Yaman Agaoglu Fulya , Ayan Inci , Darendeliler M. Emin
Published: September 2018

e22009

Background: Bilateral retinoblastomas (BRBS) comprise 25 % of all RBS. Treatment decision depends on tumor burden, potential for vision, status of the contralateral eye. As the survival rate in retinoblastoma has increased, ocular salvage and late effects has become an important issue. The aim of the study is to evaluate the demographic features, treatment modalities, and late effects in BRBS. Methods: BRBS treated in Istanbul University, Oncology Institute and Opthalmology Department between 1990-2016 were retrospectively evaluated. All patients were multidisciplinarily evaluated for chemotherapy (chemoreduction /adjuvant), local opthalmologic therapies (transpupillary thermotherapy, cryotherapy, plaque), radiotherapy, enucleation. The chemotherapy (CT) protocol used had vincristine, cisplatin, etoposide, cyclophosphamide until 2009, and vincristine, etoposide, carboplatin since then. Since 2011, intraarterial, intravitreal CT was also used. Results: 114 BRBS (228 eyes) (56 male, 58 female) with a median age of 9 months (20days-42 mo.) were evaluated. Three had extraocular disease, two trilateral RBS. Seventeen had history of retinoblastoma in their families. According to ICRB classification, there were 67 eyes in group E, 43 group D, 27 group C, 45 group B, and 19 group A. Enucleation was done in 68 (30%) eyes, mostly group E. During 1990-2000, 23/26 patients underwent enucleation, whereas 45/88 underwent enucleation after 2000. Radiotherapy was used for 30 eyes, most before 2000. Bone and soft tissue deformities and cataracts were observed in irradiated patients. Five patients had a second cancer (4 sarcomas, 1 meningioma) at a median of 11 years, four in irradiated sites. The 5 yr survival was 93.5%, 9 patients died, 4 due to second cancer. Conclusions: As the survival rate in intraocular BRBS has increased, ocular salvage and late effects have gained importance. Chemoreduction (systemic, intraarterial) and local ophtalmic therapies enable preservation of vision in most group A, B, C tumors and some D tumors. Most group E tumors require enucleation. Radiotherapy is not used in most RBS in the last decade. Intra-arterial chemotherapy is promising in maintaining ocular salvage.
Effect of infusion duration on high-dose methotrexate (HDMTX) acute kidney injury (AKI).
Authors: Fox Elizabeth , Busch Christine , DeBernardo Alexander , Levin Kristin , Zhu Yan , Bagatell Rochelle , Balamuth Naomi Jill , Womer Richard B. , Balis Frank M. ,   Children's Hospital of Philadelphia Bone and Soft Tissue Tumor Program
Published: September 2018

e22013

Background: HDMTX AKI delays MTX excretion and increases the risk for severe systemic toxicity. MTX is thought to crystalize in renal tubules at urine [MTX] above the solubility limit, leading to AKI. Methods: Pharmacokinetic simulations of plasma and urine [MTX] at varying infusion durations (IDs) for 12 g/m2 MTX dose identified 12 h as the shortest duration with urine [MTX] below the solubility limit at pH 7.5. Using a randomized crossover design, we compared 4h and 12h IDs in patients with osteosarcoma treated with 12 g/m2 MTX. Urine AKI biomarkers (NAG, NGAL, KIM-1), urinalysis, and estimated glomerular filtration rate (GFR) were endpoints. [MTX] was measured in plasma using a commercial fluorescence polarization assay and in urine by HPLC. Results: Twelve patients, age 12.8 (5.6-19) y, received 12 g/m2 HDMTX over 4 h (40 infusions) and 12 h (35 infusions). At baseline (BL), GFR was 120 (100-175) mL/min/1.73m2; Median (range) NAG [21(5-64) U/gCr] and NGAL [11(0.7-325) µg/gCr] were normal and KIM-1 [0.9(0.4-6.3) µg/gCr] was elevated. Urine pH was maintained > 7 for all infusions. Proteinuria occurred during 93% of infusions. Table 1 compares 4h and 12h IDs. One patient had HDMTX AKI during a 12 h ID (data excluded from Table); end of infusion (EOI) [MTX] was 930 µM in plasma and 38 mM in urine. By 24h after the start of the HDMTX infusion, serum creatinine (sCr) was 1.4 mg/dL (3.5x BL), cystatin C was 1.0 (1.4x BL); NAG, NGAL and Kim-1 increased by > 350%. At 40h, plasma [MTX] was 40 µM; glucarpidase was administered. Plasma [MTX] < 0.1 µM was achieved at 310 h. Recovery to BL occurred at 20 d for sCr and 40 d for cystatin C. Conclusions: Transient proteinuria, increase in KIM-1 and NAG indicate acute proximal renal tubular damage in all HDMTX infusions regardless of ID. EOI urine [MTX] after 4 h or 12 h IDs did not exceed the solubility limit, including the patient with clinical HDMTX AKI. These results suggest that MTX crystallization in urine may not be the primary mechanism of HDMTX AKI. Clinical trial information: NCT01848457. [Table: see text]
A preliminary study of apatinib in Chinese patients with osteosarcoma.
Authors: Zhou Yong , Tang Fan , Min Li , Zhang Wenli , Shi Rui , Luo Yi , Duan Hong , Tu Chongqi
Published: September 2018

e22500

Background: Osteosarcoma is the most common malignant tumor of bone that displays hyperproliferative characteristics and high vascularity, making vascular endothelial growth factor receptors (VEGFRs) become promising targets. Apatinib, a tyrosine kinase inhibitor targeting VEGFR-2, shows anti-cancer effects against a broad range of malignancies. This study reported the clinical experience of apatinib in osteosarcoma. Methods: We collected the medical data of osteosarcoma cases who received apatinib for at least one month in our hospital. The objective response rate (ORR), disease control rate (DCR), and 6-month progression-free survival (PFS) and overall survival (OS) rates were evaluated, and the safety profile was observed. The cut-off date of analysis was 01/17/2017. Results: Between May 2015 and Nov 2016, a total of 34 cases received apatinib with informed consent (4 as neoadjuvant, 1 as neoadjuvant and first line, 10 as first line, 15 as second line and 4 as third line). Among them, 18 (52.9%) cases suffered from pulmonary metastases before apatinib administration; 29 (85.3%) patients had an Eastern Cooperative Oncology Group performance status of 1–2. Initial dosages of 250, 425, and 500 mg/d were given to 5 (14.7%), 3 (8.8%), and 26 (76.5%) cases, respectively. Dosage adjustment occurred in only 8 (23.5%) patients. The median duration was 5.9 months (95%CI, 4.5–9.4 months). According to RECIST v1.1, complete response, partial response, stable disease and progressive disease were achieved in 1 (2.9%), 6 (17.6%), 25 (73.5%) and 2 (5.9%) patients, respectively. The ORR was 20.5%, and the DCR was 94.1%. Patients with pulmonary metastases showed a relatively better response to apatinib, as the ORR and DCR were 33.3% and 88.9%, respectively. As for safety analysis, the most 3 common adverse events (AEs) were hand-foot syndrome (HFS) (29, 85.3%), diarrhea (16, 47.1%), and decreased appetite (9, 26.5%). Nine grade III AEs were occurred including 3 HFS, 2 hypertension, 1 diarrhea, 1 oral mucositis, 1 proteinuria and 1 serious peeling. Conclusions: Apatinib seems to be effective in treating osteosarcoma with acceptable safety profile. Perspective clinical studies with adequate sample size are required to validate our results.
Pre-operative tomotherapy for retroperitoneal liposarcoma: Results of a phase II multicenter study.
Authors: Kantor Guy , Stoeckle Eberhard , Delannes Martine , Mahe Marc-Andre , Italiano Antoine , Kind Michèle , Dupouy Christine , Giraud Antoine , Antoine Mikael , Toulmonde Maud , Mervoyer Augustin , Ferron Gwennael , Bellera Carine A. , Sargos Paul
Published: September 2018

e22501

Background: To evaluate efficacy and feasibility of radiotherapy (RT: high-level dose 54 Gy, with 30 fractions over / 6 weeks) followed by surgery, for retroperitoneal liposarcomas. Methods: Helical tomotherapy was used for pre-operative RT. Clinical Target Volume (CTV) and main organs at risk were systematically delineated with the surgeon. Surgery was planned 4 to 8 weeks after RT. Inclusion criteria were operable, biopsy-proven, retroperitoneal liposarcomas. Toxicity was graded according to CTCAE V3.0. Overall survival (OS) was estimated using Kaplan-Meier method. Due to competing risks, we estimated the cumulative incidence of loco-regional relapse; 95% confidence intervals are reported [95%CI]. Results: Patients:From 04/2009 to 09/2013, 48 patients were included. Mean age: 62 years (y) (36 to 82). All but 1 patient were OMS ≤ 2. Histological types were 20 well differentiated (WDLS) and 28 dedifferentiated liposarcomas. Mean CTV was 2954 cc. Treatment:1 patient did not have surgery. Dosimetric constraints were respected. Monobloc exerese was systematically achieved. Surgical margins were R0 (16; 34%), R1 (28; 60%), R2 (2; 4%) or missing (1; 2%). Oncological outcomes:Median follow-up was 4.7 y. Cumulative incidence of loco-regional relapse at 3 and 5 y was 17% [8%; 29%] and 31% [16%; 47%] respectively. Estimates were 5% and 35% for dedifferentiated liposarcoma and 26% and 26% for well differentiated liposarcoma. OS at 3 and 5 y was 81% [66%; 89%]) and 78% ([63%; 88%] respectively. Toxicity: 2 months after surgery, 10 grade 3 toxicities and 1 grade 4 toxicity were reported for 6 patients; 3 patients died within 6 months after surgery, 2 of which were related to treatment. After 1 y, no further severe toxicity was observed; 5 cases of second cancers were reported: 1 myeloid leukeamia, 2 pancreatic, 2 breast carcinomas. Conclusions: This trial highlights the feasibility of preoperative 54 Gy RT. Although efficacy data (local control and OS) are encouraging, high incidence rates of acute toxicities and second cancers should be considered. Preoperative RT for WDLS remains questionable. Results from ongoing EORTC phase III Strass trial may provide further level of evidence for this approach. Clinical trial information: NCT01841047.
Response of advanced soft tissue sarcoma to apatinib: A retrospective analysis.
Authors: Yang Wuwei , Zhu Baorang , Li Jing , Xie Qiaosheng , Diao Liyan , Gai Lvhua
Published: September 2018

e22502

Background: Soft tissue sarcomas (STSs) are rare but malignant tumors with high risks of local recurrence and distant metastasis. Promising efficacy of apatinib was reported in several subtypes of STSs (Dong et al. 2016, Medicine 95: e4368; Ji et al. 2016, OncoTargets and therapy 9:643-647). We aimed to preliminarily assess the short efficacy and safety of apatinib, an oral tyrosine kinase inhibitor targeting VEFGR-2, in patients with advanced STS. Methods: The medical records of 31 patients who received apatinib between September 2015 and August 2016 were retrospectively reviewed to evaluate the short efficacy, time to progression (TTP) and safety. Results: Nineteen (61.3%) patients taken apatinib after failing second or even more lines of cytotoxic chemotherapy, 8 (25.8%) patients received apatinib as second-line therapy, and 4 (12.9%) cases who refused chemotherapy was given apatinib as first-line therapy. In the study cohort, one patient was treated with apatinib as adjunctive therapy after ablation, while the remaining 30 as salvage therapy. Administration was stopped in 6 cases due to adverse events (n = 3) or personal reasons (n = 3). As a result, 24 patients were eligible for tumor response to apatinib evaluation, and 25 patients were available for survival analysis. The objective response rate was 33.3% and clinical benefit rate was as high as 75.0%. The median TTP was 4.3 months (range, 1.8–11.6 months). Most of the AEs were at grade 1 or 2. The grade 3 AEs were hypertension (n = 2, 6.5%), hand-foot syndrome (n = 2, 6.5%), and diarrhea (n = 1, 3.2%). No grade 4 AE or drug-related mortality occurred. Conclusions: Apatinib showed promising efficacy and acceptable safety profile in metastatic or recurrent STS, giving rationale clinical evidence to conduct clinical trials.
A nonrandom association of sarcoidosis in patients with gastrointestinal stromal tumor and other sarcomas.
Authors: Espejo Freire Andrea Patricia , Ramdial Jeremy , Wilky Breelyn A. , Kerr Darcy , Trent Jonathan C.
Published: September 2018

e22521

Background: Sarcoidosis can mimic metastatic cancer. Although sarcoidosis is associated with carcinomas, there are limited data supporting its association with GIST and other sarcomas. Prior reports on cancer related sarcoidosis are inconsistent in terms of prognosis; while some reports link sarcoidosis with a favorable prognosis, others associate it with recurrence and secondary malignancies. Here we describe a series of 7 patients with diagnosis of sarcoma and sarcoidosis seen at a single sarcoma center in South Florida. Methods: Seven patients with diagnosis of both sarcoma and sarcoidosis were identified over the period of 2007 to 2016. Data of presentation, treatment, histology and outcome was tabulated for analysis. The Standardized Incidence Ratio (SIR) was calculated for the state of Florida and for our hospital catchment area. Results: Of the seven patients, 4 cases were GIST, 1 case of unclassified spindled and epithelioid cell sarcoma that coexisted with tenosynovial giant cell tumor, 1 case of uterine leiomyosarcoma, and 1 case of myxofibrosarcoma. Sarcoidosis was diagnosed before sarcoma in 3 patients, after the diagnosis of sarcoma in 3 patients and at the same time of sarcoma diagnosis in 1 patient. All cases of sarcoidosis involved the lungs. From our series, 3 patients have shown no progression of sarcoma, 1 is alive with sarcoma, 2 died due to progression of sarcoma and 1 was lost to follow up. Statistical analyses showed a SIR = 268 (95% CI 106-503), when comparing to the expected incidence in the state of Florida and SIR = 831 (95% CI 329-1562), when comparing to the expected incidence in our catchment area. Conclusions: This case series points to a statistically robust, non-random, association between Sarcoma and Sarcoidosis that has not been previously described. Our study found the lung is not only the most common site of sarcoma metastasis but also the most common site of sarcoidosis. These results infer that patients with presumed metastatic sarcoma should be considered for a biopsy to rule out a benign process such as sarcoidosis. Additionally, the presence of sarcoidosis could be associated with risk of sarcoma. The mechanism of sarcoidosis-associated sarcoma is ongoing.
Metastatic soft tissue sarcomas (STS) in elderly patients: 18 years of monoinstitutional experience.
Authors: Comandone Alessandro , Boglione Antonella , Giubellino Elena , Bergnolo Paola , chiadò Cutin Simona , Dal Canton Orietta , Garetto Ferdinando , Ottaviani Davide , Piana Raimondo , Pochettino Paolo , Prati Veronica
Published: September 2018

e22528

Background: Elderly people represent more than 50% of STS patients, but few data are available in this population and old patients in clinical studies are underrepresented or not included. Aim of this retrospective, monoinstitutional study is to describe the activity and feasibility of first and second line chemotherapy in elderly patients with metastatic STS. Methods: Patients older than 65, with metastatic STS of the scalp, trunk, girdles and extremities, treated and followed from February 1998 to December 2015 in an Italian referral Center for diagnosis and care of STS were included. Median Overall survival (OS) was the principal end point calculated from the start of chemotherapy to the last date of follow up or death. Response rate and toxicities related to type of administered chemotherapy were the secondary end points. Results: 134 patients (79 M, 55F) were considered, (65-70 y) 63%, (71- 75y) 25%, ( > 76 y)11% . STS histologies: mixoid and round cell liposarcomas (34%), leiomyosarcomas (25%), pleomorphic undifferentiated sarcomas (13%), Angiosarcoma (10%), Mixofibrosarcoma (6%), MPNST (4%), synovial sarcoma (2%), other histologies (6%). All the patients received at least one course chemotherapy (1-12). Mono CT was the preferred administered schedule (92%of cases). Median OS was 7.3 months; at the time of this analysis only 14 patients were alive (10%). In the first line therapy we recorded 1 CR, 14 PR and 43 SD. In second line therapy no CR, 4 PR, 23 SD. PR were recorded mainly in 65-70y old patients. Bad PS, low score in Comprehensive Geriatric Assesment (CGA), vulnerability, comorbidities, number of metastasis, were negative prognostic factors. No toxic death were recorded. 12% of the pts were recovered for febrile neutropenia, thrombocitopenia and mucositis . Conclusions: Our study confirms that elderly patients with metastatic STS is a difficult population to be treated. Only patients less aged, good PS, good GCA and 0-1 comorbidities can be treated with full dose of drug, generally with mono CT. Chemotherapy in elderly pts doesn’t produce a significant improvement in Median Survival and benefit observed support the routine use of citotoxic treatment in selected good performance status population.
Peritoneal metastatic desmoplastic small round cell tumor: A single institution experience.
Authors: Souza Juliana , Mendes Gelcio L. Q.
Published: September 2018

e22541

Background: Desmoplastic small round cell tumor (DSRCT) is a rare and highly aggressive tumor that usually occurs in young males. The treatment remains a challenge and despite multiple strategies the tumor leads to death in most cases. Methods: Patients with peritoneal and metastatic DSRCT treated at or referred to National Cancer Institute of Brazil with histological documented diagnosis between July 1997 and September 2014 were identified and their medical records were analyzed. Results: There were 17 patients, the median age of diagnosis was 14.8 years (range: 4-49), with male-female ratio of 3.25. The most common sites of metastasis were liver (n: 7; 53.8%), lung (n: 6; 35%) and both (n: 2; 11.7%). Eight patients (47%) received radiotherapy and 15 patients (88.2%) received chemotherapy, 13 received vincristine, cyclophosphamide, doxorubicin and regimen with or without ifosfamide and etoposide. The median number of cycles received was 12.9 (range:1-27). Three patients (17.6%) who underwent to surgery, received the three treatments. Two patients received only palliative care. After median follow-up of 74 months, 13 patients (76.4%) died, nine patients during the first 2 years. The median overall survival was 16 months. One 6-year old patient was alive after 74 months, after chemotherapy, radiotherapy and surgery. Conclusions: The DSCRT is a rare disease with poor prognosis and high morbidity, that demand an aggressive approach. However, most patients are diagnosed with advanced disease, receiving noncurative approach.